Suggests that the Luso-Brazilian Accord is a strategy to spread the Portuguese language in Africa, particularly in the former colonies of Angola, Mozambique, Guinea-Bissau, Cape Verde, and Sao Tome e Principe, and to construct and solidify a community of lusophone nations in geopolitical terms in world affairs. Language planning in these countries…

Brazilian physician and researcher Henrique da Rocha Lima was born in 1879 in the city of Rio de Janeiro, where he studied medicine and obtained the degree of M.D. in 1901. He specialized in Clinical Medicine in Germany and was the ambassador in European countries of the scientific medicine that emerged from the Oswaldo Cruz Institute in the early twentieth century. Rocha Lima has discovered the causative agent of typhus and had a major contribution to the studies of yellow fever, Chagas disease, Carrión's disease and histoplasmosis. His genius, his research and his discoveries projected his name, and, with it, the image of Brazil in the international scientific scene.

Berengario da Carpi was magister of anatomy and surgery at the University of Bologna from 1502 to 1527. Eustachio and Falloppia defined him as 'the restaurator of anatomy'. He was a great surgeon, anatomist and physician of illustrious patients including Lorenzo II dei Medici, Giovanni dalle Bande Nere, Galeazzo Pallavicini, Cardinal Colonna, and Alessandro Soderini. He had strong links to the intellectuals of his time (Forni, Bonamici, Manuzio, Pomponazzi) as well as with the Medici family. He was respected by the Popes Julius II, Leo X and Clement VII. His main contributions are the Isogogae Breves, De Fractura calvae sive cranei, and the illustrated Commentaria on the Anatomy of Mondino de Liucci, a textbook utilized for more than 200 years, which Berengario aimed to restore to its initial text. The Commentaria constitutes the material for the last part of this paper which concludes with a personal translation of some passages on 'The kidney', where the author gives poignant examples of experimental ingenuity.

Brazilian physician and researcher Henrique da Rocha Lima was born in 1879 in the city of Rio de Janeiro, where he studied medicine and obtained the degree of M.D. in 1901. He specialized in Clinical Medicine in Germany and was the ambassador in European countries of the scientific medicine that emerged from the Oswaldo Cruz Institute in the early twentieth century. Rocha Lima has discovered the causative agent of typhus and had a major contribution to the studies of yellow fever, Chagas disease, Carrión’s disease and histoplasmosis. His genius, his research and his discoveries projected his name, and, with it, the image of Brazil in the international scientific scene. PMID:26131867

Evidence from the drawings, experiments, and writings of Leonardo da Vinci are presented to demonstrate that da Vinci recognized and, possibly, discovered the downburst and understood its associated airflow. Other early references to vortex flows resembling downbursts are mentioned.

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity.

Quantitative structure-activity relationship (QSAR) is a branch of computer aided drug discovery that relates chemical structures to biological activity. Two well established and related QSAR descriptors are two- and three-dimensional autocorrelation (2DA and 3DA). These descriptors encode the relative position of atoms or atom properties by calculating the separation between atom pairs in terms of number of bonds (2DA) or Euclidean distance (3DA). The sums of all values computed for a given small molecule are collected in a histogram. Atom properties can be added with a coefficient that is the product of atom properties for each pair. This procedure can lead to information loss when signed atom properties are considered such as partial charge. For example, the product of two positive charges is indistinguishable from the product of two equivalent negative charges. In this paper, we present variations of 2DA and 3DA called 2DA_Sign and 3DA_Sign that avoid information loss by splitting unique sign pairs into individual histograms. We evaluate these variations with models trained on nine datasets spanning a range of drug target classes. Both 2DA_Sign and 3DA_Sign significantly increase model performance across all datasets when compared with traditional 2DA and 3DA. Lastly, we find that limiting 3DA_Sign to maximum atom pair distances of 6 Å instead of 12 Å further increases model performance, suggesting that conformational flexibility may hinder performance with longer 3DA descriptors. Consistent with this finding, limiting the number of bonds in 2DA_Sign from 11 to 5 fails to improve performance.

We present computing methods that allow us to study the behaviour of the dynamically interesting potentially dangerous asteroid 2012 DA14. Using the freely available ORBFIT software, we can follow the orbit of the asteroid backward and forward in the future, searching for close approaches to the Earth that might lead to possible impacts. The possible impact orbit for 2026 is computed. We show that it should be possible to recover asteroid 2012 DA14, mainly in 2013 February. It is highly unlikely that asteroid 2012 DA14 will hit any geosynchronous satellites during its close approach on 2013 February 15.

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

Classification studies are widely applied, e.g. in biomedical research to classify objects/patients into predefined groups. The goal is to find a classification function/rule which assigns each object/patient to a unique group with the greatest possible accuracy (classification error). Especially in gene expression experiments often a lot of variables (genes) are measured for only few objects/patients. A suitable approach is the well-known method PLS-DA, which searches for a transformation to a lower dimensional space. Resulting new components are linear combinations of the original variables. An advancement of PLS-DA leads to PPLS-DA, introducing a so called 'power parameter', which is maximized towards the correlation between the components and the group-membership. We introduce an extension of PPLS-DA for optimizing this power parameter towards the final aim, namely towards a minimal classification error. We compare this new extension with the original PPLS-DA and also with the ordinary PLS-DA using simulated and experimental datasets. For the investigated data sets with weak linear dependency between features/variables, no improvement is shown for PPLS-DA and for the extensions compared to PLS-DA. A very weak linear dependency, a low proportion of differentially expressed genes for simulated data, does not lead to an improvement of PPLS-DA over PLS-DA, but our extension shows a lower prediction error. On the contrary, for the data set with strong between-feature collinearity and a low proportion of differentially expressed genes and a large total number of genes, the prediction error of PPLS-DA and the extensions is clearly lower than for PLS-DA. Moreover we compare these prediction results with results of support vector machines with linear kernel and linear discriminant analysis.

We present 16 new, and confirm 7 previously identified, DA white dwarfs in the Kepler field through ground-based spectroscopy with the Hale 200″, Kitt Peak 4-m, and Bok 2.3-m telescopes. Using atmospheric models, we determine their effective temperatures and surface gravities to constrain their position with respect to the ZZ Ceti (DA pulsator) instability strip, and look for the presence or absence of pulsation with Kepler's unprecedented photometry. Our results are as follows. (i) From our measurements of temperature and surface gravity, 12 of the 23 DA white dwarfs from this work fall well outside of the instability strip. The Kepler photometry available for 11 of these WDs allows us to confirm that none are pulsating. One of these 11 happens to be a presumed binary, KIC 11604781, with a period of ˜5 d. (ii) The remaining 11 DA white dwarfs are instability strip candidates, potentially falling within the current, empirical instability strip, after accounting for uncertainties. These WDs will help constrain the strip's location further, as eight are near the blue edge and three are near the red edge of the instability strip. Four of these WDs do not have Kepler photometry, so ground-based photometry is needed to determine the pulsation nature of these white dwarfs. The remaining seven have Kepler photometry available, but do not show any periodicity on typical WD pulsation time-scales.

To be effective and relevant in twenty-first-century learning, art needs to be more inclusive. In this article, the author discusses how teachers can find a good example in Leonardo da Vinci for building an art program. His art, design, and curiosity are the perfect foundation for any art program, at any level. (Contains 3 resources and 3 online…

Three drawings on the back of Leonardo da Vinci's The Virgin and Child with St Anne (circa 1508) have been discovered by researchers led by Michel Menu from the Centre de Recherche et de Restauration des Musées de France (C2RMF) and the Louvre Museum in Paris.

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes.

When a company name means "giving life," the bar for learning and development programs is held high. In this article, the author describes what it takes to graduate from DaVita Academy, the soft skills training program dialysis services company DaVita offers all its employees. DaVita's chief executive officer, Kent Thiry, states that the Academy…

PanDA (Production and Distributed Analysis System) is a workload management system, widely used for data processing at experiments on Large Hadron Collider and others. COMPASS is a high-energy physics experiment at the Super Proton Synchrotron. Data processing for COMPASS runs locally at CERN, on lxbatch, the data itself stored in CASTOR. In 2014 an idea to start running COMPASS production through PanDA arose. Such transformation in experiment's data processing will allow COMPASS community to use not only CERN resources, but also Grid resources worldwide. During the spring and summer of 2015 installation, validation and migration work is being performed at JINR. Details and results of this process are presented in this paper.

We present a radio continuum study of the pulsar wind nebula (PWN) DA 495 (G65.7+1.2), including images of total intensity and linear polarization from 408 to 10550 MHz based on the Canadian Galactic Plane Survey and observations with the Effelsberg 100 m Radio Telescope. Removal of flux density contributions from a superimposed H II region and from compact extragalactic sources reveals a break in the spectrum of DA 495 at 1.3 GHz, with a spectral index α = - 0.45 +/- 0.20 below the break and α = - 0.87 +/- 0.10 above it (Sν propto να). The spectral break is more than 3 times lower in frequency than the lowest break detected in any other PWN. The break in the spectrum is likely the result of synchrotron cooling, and DA 495, at an age of ~20,000 yr, may have evolved from an object similar to the Vela X nebula, with a similarly energetic pulsar. We find a magnetic field of ~1.3 mG inside the nebula. After correcting for the resulting high internal rotation measure, the magnetic field structure is quite simple, resembling the inner part of a dipole field projected onto the plane of the sky, although a toroidal component is likely also present. The dipole field axis, which should be parallel to the spin axis of the putative pulsar, lies at an angle of ~50° east of the north celestial pole and is pointing away from us toward the southwest. The upper limit for the radio surface brightness of any shell-type supernova remnant emission around DA 495 is Σ1GHz ~ 5.4 × 10-23 W m-2 Hz-1 sr-1 (assuming a radio spectral index of α = - 0.5), lower than the faintest shell-type remnant known to date.

Leonardo da Vinci's texts consist almost exclusively of scientific notes. Working on a book on Leonardo's art, I studied all Leonardo's published texts carefully for any new information. In some prefaces I came to suspect that Leonardo might have suffered from dyslexia. This article considers the question of whether it is possible to find indications of dyslexia in Leonardo's texts and in the accounts of his life.

Leonardo da Vinci's detailed drawings are justly celebrated; however, less well known are his accounts of the structures and functions of the organs. In this paper, we focus on his illustrations of the heart, his conjectures about heart and blood vessel function, his experiments on model systems to test those conjectures, and his unprecedented conclusions about the way in which the cardiovascular system operates. In particular, da Vinci seems to have been the first to recognize that the heart is a muscle and that systole is the active phase of the pump. He also seems to have understood the functions of the auricles and pulmonary veins, identified the relationship between the cardiac cycle and the pulse, and explained the hemodynamic mechanism of valve opening and closure. He also described anatomical variations and changes in structure and function that occurred with age. We outline da Vinci's varied career and suggest ways in which his personality, experience, skills and intellectual heritage contributed to these advances in understanding. We also consider his influence on later studies in anatomy and physiology.

The spectral coverage of a light-harvesting polymer largely determines the maximum achievable photocurrent in organic photovoltaics, and therefore constitutes a crucial parameter for improving their performance. The D-A1-D-A2 copolymer motif is a new and promising design strategy for extending the absorption range by incorporating two acceptor units with complementary photoresponses. The fundamental factors that promote an extended absorption are here determined for three prototype D-A1-D-A2 systems through a combination of experimental and computational methods. Systematic quantum chemical calculations are then used to reveal the intrinsic optical properties of ten further D-A1-D-A2 polymer candidates. These investigated polymers are all predicted to exhibit intense primary absorption peaks at 615-954 nm, corresponding to charge-transfer (CT) transitions to the stronger acceptor, as well as secondary absorption features at 444-647 nm that originate from CT transitions to the weaker acceptors. Realization of D-A1-D-A2 polymers with superior spectral coverage is thereby found to depend critically on the spatial and energetic separation between the two distinct acceptor LUMOs. Two promising D-A1-D-A2 copolymer candidates were finally selected for further theoretical and experimental study, and demonstrate superior light-harvesting properties in terms of significantly extended spectral coverage. This demonstrates great potential for enhanced light-harvesting in D-A1-D-A2 polymers via multiple absorption features compared to traditional D-A polymers.

This paper describes a novel digital-to-analog (D/A) conversion technique, which uses the analog quantity polarization as a D/A conversion medium. It can be implemented by CMOS capacitors or by ferroelectric capacitors, which exhibit strong nonlinearity in charge versus voltage behavior. Because a ferroelectric material inherently has spontaneous polarization and generally has a large dielectric constant, the effective capacitance of a ferroelectric capacitor is much larger than that of a CMOS capacitor of the same size. This ensures less influence of bottom-electrode parasitic capacitance on a ferroelectric capacitor. Furthermore, a data converter based on ferroelectric capacitors possesses the potential nonvolatile memory function owing to ferroelectric hysteresis. Along with the architecture proposed for polarization-switching digital-to-analog converter (PDAC), its circuit implementation is introduced. Described is implementation of two 9-bit bipolar PDACs: one is based on CMOS capacitors and the other on off-chip ferroelectric capacitors. Experimental results are presented for the performance of these two prototypes.

The Bunche-Da Vinci case described in this article presents a situation at Bunche Elementary School that four theorists were asked to address in their evaluation designs (see EJ791771, EJ719772, EJ791773, and EJ792694). The Bunche-Da Vinci Learning Partnership Academy, an elementary school located between an urban port city and a historically…

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.

The syndrome variously called Da Costa's syndrome, effort syndrome, neurocirculatory asthenia, etc has been studied for more than 100 years by many distinguished physicians. Originally identified in men in wartime, it has been widely recognised as a common chronic condition in both sexes in civilian life. Although the symptoms may seem to appear after infections and various physical and psychological stresses, neurocirculatory asthenia is most often encountered as a familial disorder that is unrelated to these factors, although they may aggravate an existing tendency. Respiratory complaints (including breathlessness, with and without effort, and smothering sensations) are almost universal, and palpitation, chest discomfort, dizziness and faintness, and fatigue are common. The physical examination is normal. The aetiology is obscure but patients usually have a normal life span. Reassurance and measures to improve physical fitness are helpful. PMID:3314950

Leonardo da Vinci (1452-1519) made far-reaching contributions to many areas of science, technology and art. Leonardo's pioneering research into the brain led him to discoveries in neuroanatomy (such as those of the frontal sinus and meningeal vessels) and neurophysiology (he was the first to pith a frog). His injection of hot wax into the brain of an ox provided a cast of the ventricles, and represents the first known use of a solidifying medium to define the shape and size of an internal body structure. Leonardo developed an original, mechanistic model of sensory physiology. He undertook his research with the broad goal of providing physical explanations of how the brain processes visual and other sensory input, and integrates that information via the soul.

Recent advances in the determination of the hot white dwarf (WD) luminosity function have reached the point where we have good agreement between the observed and theoretical DA and non-DA LFs for WDs from SDSS DR4. The main progress in calculation of the DA LF was obtained when the WD sample was restricted to only carbon-oxygen core WDs. However, one remaining effect which could influence the LF and the non-DA to DA ratio is the difference in visibility of helium- and hydrogen-atmosphere WDs in a magnitude-limited sample. In this work we explore this effect for the SDSS g filter as a function of effective temperature, as well as make an attempt to evaluate data relevant to the WD sample and LFs from more recent data releases of the SDSS.

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule.

The Self-Assessment Comparison (SAC) Tool is for state Part C and Section 619/Preschool programs to use to assess changes in the implementation of one or more components of the ECTA System Framework and/or subcomponenets of the DaSy Data System Framework. It is a companion to the ECTA/DaSy Framework Self-Assessment. Key features of the SAC are…

Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

The ATLAS Production and Distributed Analysis System (PanDA) is a key component of the ATLAS distributed computing infrastructure. All ATLAS production jobs, and a substantial amount of user and group analysis jobs, pass through the PanDA system, which manages their execution on the grid. PanDA also plays a key role in production task definition and the data set replication request system. PanDA has recently been migrated from Brookhaven National Laboratory (BNL) to the European Organization for Nuclear Research (CERN), a process we describe here. We discuss how the new infrastructure for PanDA, which relies heavily on services provided by CERN IT, was introduced in order to make the service as reliable as possible and to allow it to be scaled to ATLAS's increasing need for distributed computing. The migration involved changing the backend database for PanDA from MySQL to Oracle, which impacted upon the database schemas. The process by which the client code was optimised for the new database backend is discussed. We describe the procedure by which the new database infrastructure was tested and commissioned for production use. Operations during the migration had to be planned carefully to minimise disruption to ongoing ATLAS offline computing. All parts of the migration were fully tested before commissioning the new infrastructure and the gradual migration of computing resources to the new system allowed any problems of scaling to be addressed.

This work presents DaTo, a semi-automatically generated world atlas of biological databases and tools. It extracts raw information from all PubMed articles which contain exact URLs in their abstract section, followed by a manual curation of the abstract and the URL accessibility. DaTo features a user-friendly query interface, providing extensible URL-related annotations, such as the status, the location and the country of the URL. A graphical interaction network browser has also been integrated into the DaTo web interface to facilitate exploration of the relationship between different tools and databases with respect to their ontology-based semantic similarity. Using DaTo, the geographical locations, the health statuses, as well as the journal associations were evaluated with respect to the historical development of bioinformatics tools and databases over the last 20 years. We hope it will inspire the biological community to gain a systematic insight into bioinformatics resources. DaTo is accessible via http://bis.zju.edu.cn/DaTo/.

Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as AUXIN RESPONSE FACTOR2, APETALA2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) GRAIN WIDTH AND WEIGHT2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement. PMID:24045020

The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect.

Thioredoxins (TRX) are ubiquitous, small redox-active proteins with multiple functions, including antioxidant, cytoprotective, and chemoattractant activities. In addition to a 12-kDa intracellular form, extracellular 10-kDa and 12-kDa TRX have been defined. The biological activities of the 10-kDa TRX were previously measured as eosinophil cytotoxicity enhancing activity or B-cell stimulatory activity. Cytotrophoblastic cell lines also release a 10-kDa TRX form. To study the biological role of 10-kDa TRX, we established two highly sensitive enzyme-linked immuno-spot assays (ELISPOT), which detect secreted truncated 10-kDa and full-length 12-kDa TRX at the single cell level. TRX secretion was investigated in several cell lines including the T-helper cell hybridoma MP6, the Jurkat T-cell leukemia, the U-937 myelomonocytic leukemia, and the 3B6, EBV-transformed, lymphoblastoid B-cell line. The highest number of secreting cells was found in 3B6 cultures, median = 34 (quartiles, 27-39) per well (10(5) cells). Peripheral blood monocytes isolated from healthy donors secreted significantly more TRX after stimulation with ionomycin, phorbol myristate acetate (PMA), fMLP, and lipopolysaccharide (LPS), compared to unstimulated cells. Oxidative stress induced by thioloxidant diamide also induced the secretion of both truncated and full-length TRX measured in ELISPOT (p = 0.047 and p = 0.031, respectively). The biological activity of the truncated and full-length forms was tested in a cell migration assay. Truncated TRX was devoid of protein disulfide reductase activity, but retained strong chemoattractant activity for human monocytes, in the same range as full-length TRX, as previously reported (Bertini et al., 1999).

Two molecular forms of the muscarinic cholinergic receptor have been consistently observed in a variety of species, albeit in variable amounts. Proteins which are specifically labeled by (/sup 3/H)propylbenzilylcholine mustard ((/sup 3/H)PrBCM) were observed at 94kDa and 80kDa upon SDS-PAGE of membrane proteins prepared from brains and hearts of trout, frog, turtle, chicken, rat, and pig. They have developed a purification procedure which yields each of these proteins in a homogeneous form suitable for structural analysis. The four step procedure involves affinity chromatography on 3-(2'-aminobenzhydryloxy)tropane-sepharose, concentration on hydroxylapatite, preparative SDS-PAGE and extraction of individual bands from the gel. Limited tryptic digestion of purified (/sup 3/H)PrBCM-labeled porcine atrial muscarinic receptor yields (/sup 3/H)-labeled fragments of 75, 65, 52, 40, 35, 30, 25, and 20kDa, in close agreement with results of analogous digestions of muscarinic receptor from other species and tissues. Complete tryptic digestion and subsequent mapping by reverse-phase HPLC yields very similar profiles for (/sup 125/I)-labeled 94kDa and 80kDA receptor forms. Most peaks which elute in the hydrophobic region of the profile overlap for the two proteins while the 94kDa protein contains several additional peaks of apparent low hydrophobicity.

... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; Diamond Aircraft... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been replaced because of damage found on the hinge. Diamond Aircraft Industries conducted analyses...

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in addition to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.

The PanDA (Production and Distributed Analysis) Workload Management System is used for ATLAS distributed production and analysis worldwide. The needs of ATLAS global computing imposed challenging requirements on the design of PanDA in areas such as scalability, robustness, automation, diagnostics, and usability for both production shifters and analysis users. Through a system-wide job database, the PanDA monitor provides a comprehensive and coherent view of the system and job execution, from high level summaries to detailed drill-down job diagnostics. It is (like the rest of PanDA) an Apache-based Python application backed by Oracle. The presentation layer is HTML code generated on the fly in the Python application which is also responsible for managing database queries. However, this approach is lacking in user interface flexibility, simplicity of communication with external systems, and ease of maintenance. A decision was therefore made to migrate the PanDA monitor server to Django Web Application Framework and apply JSON/AJAX technology in the browser front end. This allows us to greatly reduce the amount of application code, separate data preparation from presentation, leverage open source for tools such as authentication and authorization mechanisms, and provide a richer and more dynamic user experience. We describe our approach, design and initial experience with the migration process.

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in addition to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.

Asteroidal object 1991 DA has an orbit of high inclination, crossing the planets from Mars to Uranus. This is unique for an asteroid, but not unusual for a comet of the Halley-type: it therefore seems likely that 1991 DA is an extinct or dormant comet. Previous CCD imaging has shown no indication of a coma; spectroscopic observations of 1991 DA which lack any evidence of strong comet-like emissions are reported. Numerical integrations of the orbit of this object were performed which show that is has been remarkably stable for the past approximately 20,000 yr, but chaotic before that. This may allow a new estimate to be made of the physical lifetimes of comets.

Few geomagnetic ground observations exist of the Earth's strongest core field anomaly, the South Atlantic Anomaly (SAA). The geomagnetic repeat station on the island Tristan da Cunha, located half-way between South Africa and South America at 37?? 05' S, 12?? 18' W, is therefore of crucial importance. We have conducted several sets of repeat station measurements during magnetically quiet conditions (Kp 2o or less) in 2004. The procedures are described and the results are compared to those from earlier campaigns and to the predictions of various global field models. Features of the local crustal bias field and the solar quiet daily variation are discussed. We also evaluate the benefit of continuous magnetic field recordings from Tristan da Cunha, and argue that such a data set is a very valuable addition to geomagnetic satellite data. Recently, funds were set up to establish and operate a magnetometer station on Tristan da Cunha during the Swarm magnetic satellite mission (2011-2014).

Experiments at the Large Hadron Collider (LHC) face unprecedented computing challenges. Heterogeneous resources are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, while data processing requires more than a few billion hours of computing usage per year. The PanDA (Production and Distributed Analysis) system was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. In the process, the old batch job paradigm of locally managed computing in HEP was discarded in favour of a far more automated, flexible and scalable model. The success of PanDA in ATLAS is leading to widespread adoption and testing by other experiments. PanDA is the first exascale workload management system in HEP, already operating at more than a million computing jobs per day, and processing over an exabyte of data in 2013. There are many new challenges that PanDA will face in the near future, in addition to new challenges of scale, heterogeneity and increasing user base. PanDA will need to handle rapidly changing computing infrastructure, will require factorization of code for easier deployment, will need to incorporate additional information sources including network metrics in decision making, be able to control network circuits, handle dynamically sized workload processing, provide improved visualization, and face many other challenges. In this talk we will focus on the new features, planned or recently implemented, that are relevant to the next decade of distributed computing workload management using PanDA.

GAVO's Data Center Helper Suite (DaCHS) is a suite of tools for publishing data to the Virtual Observatory. It implements all major VO protocols (SCS, SIAP, SSAP, TAP, OAI-PMH). The integrated management and ingestion component allow defining metadata, structure, and services once and re-use the definition throughout the publication cycle from initial metadata aquisition to registry record generation. It has been driving GAVO's data center since 2008 and is now deployed in multiple locations around the globe. This poster briefly describes the design of the system as well as a bird's-eye view of data publishing with DaCHS.

Four widely used photometric systems, namely the Johnson-Kron-Cousins UBVRI, the Strömgren uvby, the 2MASS JHKs and the Sloan Digital Sky Survey ugriz systems have been directly compared with the HST absolute photometric scale of Bohlin & Gilliland (2004). These comparisons are subsequently used to construct a large grid of accurate synthetic magnitudes for DA white dwarfs. This grid is, in turn, critically evaluated with respect to the observed photometry from substantial samples of actual white dwarfs. The advantages of DA white dwarfs as photometric stars are emphasized, and the prospects for extending the use of these stars into the near infrared are highlighted.

... used in combined cycle systems, either of the procedures described in paragraph (j)(1) or (2) of this... (O2) (or carbon dioxide (CO2)) and meet the requirements of § 60.49Da. Alternatively, data from a NOX... shall constitute the NOX emission rate from the duct burner of the combined cycle system. (k)...

... combined cycle systems, either of the procedures described in paragraph (j)(1) or (2) of this section may... carbon dioxide (CO2)) and meet the requirements of § 60.49Da. Alternatively, data from a NOX emission... shall constitute the NOX emission rate from the duct burner of the combined cycle system. (k)...

... using the CEMS specified under § 60.49Da for measuring NOX and oxygen (O2) (or carbon dioxide (CO2)) and... using electronic or other means (e.g., using a strip chart recorder or a data logger.) (C) The bag...

...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Electric Utility Steam Generating Units for Which Construction is Commenced After September 18, 1978 § 60.51Da Reporting... the quarter; reasons for non-compliance with the emission standards; and, description of...

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles recent successful examples of students studying and working abroad as part of the European Commission's Leonardo da Vinci program, which is designed to give students across the European Union the opportunity to experience vocational training in a foreign country. The following examples are presented: (1) 3 Finnish students…

Provides an overview of the DaVinci Project, a collaboration of students, teachers, and researchers in chemistry and art to develop multimedia materials for grades 3-12 visualizing basic concepts in chemistry and visual art. Topics addressed include standards in art and science; the conceptual framework for the project; and project goals,…

The study of the human form is fundamental to both science and art curricula. For vertebrates, perhaps no feature is more important than the skeleton to determine observable form and function. As Leonard da Vinci's famous Proportions of the Human Figure (Virtruvian Man) illustrates, the size, shape, and proportions of the human body are defined by…

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles programs in the fields of health and medicine that are offered through the European Commission's Leonardo da Vinci program. The following programs are profiled: (1) CYTOTRAIN (a transnational vocational training program in cervical cancer screening); (2) Apollo (a program of open and distance learning for paramedical…

Metabolic engineering is often facilitated by cloning of genes encoding enzymes from various heterologous organisms into E. coli. Such engineering efforts are frequently hampered by foreign genes that are toxic to the E. coli host. We have developed PanDaTox (www.weizmann.ac.il/pandatox), a web-based resource that provides experimental toxicity information for more than 1.5 million genes from hundreds of different microbial genomes. The toxicity predictions, which were extensively experimentally verified, are based on serial cloning of genes into E. coli as part of the Sanger whole genome shotgun sequencing process. PanDaTox can accelerate metabolic engineering projects by allowing researchers to exclude toxic genes from the engineering plan and verify the clonability of selected genes before the actual metabolic engineering experiments are conducted.

The family of small heat shock proteins is the more variable among the highly conserved superfamily of heat shock proteins (HSP). Using a metabolic labeling procedure with tissue explants, we have detected in chickens a new member of the small HSP family with an apparent molecular weight of 29-kDa. This protein was induced in broiler chickens' heart muscle and lungs following an in vivo heat stress. The 29-kDa band appears after 3 h of heat stress, much later than the induction of HSP 90, HSP 70, and HSP 27. The late onset of induction suggests that HSP 29 plays a more specific role of a "second stage defense protein".

We present the Tool for Astrophysical Data Analysis (TA-DA), a new software aimed to greatly simplify and improve the analysis of stellar photometric data in comparison with theoretical models, and allow the derivation of stellar parameters from multi-band photometry. Its flexibility allows one to address a number of such problems: from the interpolation of stellar models, or sets of stellar physical parameters in general, to the computation of synthetic photometry in arbitrary filters or units; from the analysis of observed color-magnitude diagrams to a Bayesian derivation of stellar parameters (and extinction) based on multi-band data. TA-DA is available as a pre-compiled Interactive Data Language widget-based application; its graphical user interface makes it considerably user-friendly. In this paper, we describe the software and its functionalities.

For several of Leonardo da Vinci's paintings, such as The Virgin and Child with St Anne or the Mona Lisa, there exist copies produced by his own studio. In case of the Mona Lisa, a quite exceptional, rediscovered studio copy was presented to the public in 2012 by the Prado Museum in Madrid. Not only does it mirror its famous counterpart superficially; it also features the very same corrections to the lower layers, which indicates that da Vinci and the 'copyist' must have elaborated their panels simultaneously. On the basis of subjective (thirty-two participants estimated painter-model constellations) as well as objective data (analysis of trajectories between landmarks of both paintings), we revealed that both versions differ slightly in perspective. We reconstructed the original studio setting and found evidence that the disparity between both paintings mimics human binocular disparity. This points to the possibility that the two Giocondas together might represent the first stereoscopic image in world history.

We have calibrated four major ground-based photometric systems with respect to the Hubble Space Telescope absolute flux scale, which is defined by Vega and four fundamental DA white dwarfs. These photometric systems include the Johnson-Kron-Cousins UBVRI, the Stromgren uvby filters, the 2MASS JHKs and the Sloan Digital Sky Survey ugriz filters. Synthetic magnitudes are calculated from model white dwarf spectra folded through the published filter response functions, these magnitudes in turn are absolutely calibrated with respect to the HST flux scale. Effective zero magnitude fluxes and zero point offsets of each system are determined. In order to verify the external observational consistency as well as to demonstrate the applicability of these definitions, the synthetic magnitudes are compared with the respective observed magnitudes of larger sets of DA white dwarfs that have well determined effective temperatures and surface gravities and which span a wide range in both of these parameters.

We usually display a laid-back approach to medical jargon throughout our theatre work. The word 'perioperative' is built from the Greek word 'peri' (around) and the Latin 'operari' (to work). Latin and Greek became the prefixed language of choice for Leonardo da Vinci, and his research was pivotal in determining the way in which surgical procedures are documented. Ancient manuscripts aided the unfolding of the secrets of anatomy, and Leonardo revealed that art was the key in expressive detailed explanation.

meteor until stony or metallic material remnants make it to the surface of the planet in which case they become meteorites . Theoretically, the...passing in close proximity to the planet are a daily manifestation. In fact within days of the 2012 DA14 transit of the planet a large meteorite entered...although meteorites approximately basketball size hit the Earth about once per day, and objects the size of an automobile reach us roughly on a weekly

The security challenges faced by users of the grid are considerably different to those faced in previous environments. The adoption of pilot jobs systems by LHC experiments has mitigated many of the problems associated with the inhomogeneities found on the grid and has greatly improved job reliability; however, pilot jobs systems themselves must then address many security issues, including the execution of multiple users' code under a common 'grid' identity. In this paper we describe the improvements and evolution of the security model in the ATLAS PanDA (Production and Distributed Analysis) system. We describe the security in the PanDA server which is in place to ensure that only authorized members of the VO are allowed to submit work into the system and that jobs are properly audited and monitored. We discuss the security in place between the pilot code itself and the PanDA server, ensuring that only properly authenticated workload is delivered to the pilot for execution. When the code to be executed is from a 'normal' ATLAS user, as opposed to the production system or other privileged actor, then the pilot may use an EGEE developed identity switching tool called gLExec. This changes the grid proxy available to the job and also switches the UNIX user identity to protect the privileges of the pilot code proxy. We describe the problems in using this system and how they are overcome. Finally, we discuss security drills which have been run using PanDA and show how these improved our operational security procedures.

In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

Data assimilation methods provide a means to handle the modeling errors and uncertainties in sophisticated ocean models. In this study, we have created an OpenDA-NEMO framework unlocking the data assimilation tools available in OpenDA for use with NEMO models. This includes data assimilation methods, automatic parallelization, and a recently implemented automatic localization algorithm that removes spurious correlations in the model based on uncertainties in the computed Kalman gain matrix. We have set up a twin experiment where we assimilate sea surface height (SSH) satellite measurements. From the experiments, we can conclude that the OpenDA-NEMO framework performs as expected and that the automatic localization significantly improves the performance of the data assimilation algorithm by successfully removing spurious correlations. Based on these results, it looks promising to extend the framework with new kinds of observations and work on improving the computational speed of the automatic localization technique such that it becomes feasible to include large number of observations.

The Production and Distributed Analysis system (PanDA) [1-2] was designed to meet ATLAS [3] requirements for a data-driven workload management system capable of operating at LHC data processing scale. Submitted jobs are executed on worker nodes by pilot jobs sent to the grid sites by pilot factories. This paper provides an overview of the PanDA pilot [4] system and presents major features added in light of recent operational experience, including multi-job processing, advanced job recovery for jobs with output storage failures, gLExec [5-6] based identity switching from the generic pilot to the actual user, and other security measures. The PanDA system serves all ATLAS distributed processing and is the primary system for distributed analysis; it is currently used at over 100 sites worldwide. We analyze the performance of the pilot system in processing real LHC data on the OSG [7], EGI [8] and Nordugrid [9-10] infrastructures used by ATLAS, and describe plans for its evolution.

Motivation: Trimeric autotransporter adhesins (TAAs), such as Yersinia YadA, Neisseria NadA, Moraxella UspAs, Haemophilus Hia and Bartonella BadA, are important pathogenicity factors of proteobacteria. Their high sequence diversity and distinct mosaic-like structure lead to difficulties in the annotation of their sequences. These stem from the large number of short repeats, the presence of compositionally unusual coiled-coils, fuzzy domain boundaries and regions of seemingly low sequence complexity. Results: We have developed a workflow, named daTAA, for the accurate domain annotation of TAAs. Its core consists of manually curated alignments and of knowledge-based rules that enhance assignments made by sequence similarity. Compared to general domain annotation servers such as PFAM, daTAA captures more domains and provides more sensitive domain detection, as well as integrated and detailed coiled-coil assignments. Availability: The daTAA server is freely accessible at http://toolkit.tuebingen.mpg.de/dataa Contact: andrei.lupas@tuebingen.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:18397894

Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

The "Colóquios dos simples e drogas he cousas medicinais de Índia" (Conversations on the simples, drugs and medicinal substances of India) (1563) of Garcia da Orta is a botanical and pharmacognosy book. The author is a Portuguese physician who studied in the Spanish universities and practiced medicine mainly in India. He studies in short chapters presented in the form of dialogues about sixty simples. Sources to which he refers are indicative of a "classical" training, but also the mark of a curious and open mind to different cultures. The Arabic sources are numerous and mainly concern the identification of substances by abundant synonyms of their names in foreign languages and different medicinal uses that may have been done by the ancient physicians. However, Da Orta is critical with respect to these sources, seeking contradictions and differences of opinion among authors. He confronts them with the oral information collected thanks to a wide network of contacts.

Dopamine (DA) produces a natriuretic/diuretic response in the kidney by mechanisms that are still not well understood. There is some indication that DA{sub 2} receptors may be involved in mediating the effects of DA, but little is known regarding the nature of this receptor in the kidney. Autoradiographic localization of ({sup 3}H)spiperone, a DA{sub 2} antagonist, indicated that high-density binding was restricted to inner medullary collecting ducts (IMCDs). ({sup 3}H)Spiperone binding was saturable, high affinity and high density. Functionally, DA stimulated prostaglandin E{sub 2} production by IMCD cells, an effect that could be blocked by the DA{sub 2} antagonist domperidone. These results indicate that the kidney inner medulla expresses a functional DA receptor that may represent a newly identified DA receptor subtype (here designated DA{sub 2K}). Moreover, these results suggest that the kidney inner medulla may be a significant site at which DA, either directly or indirectly, influences water and electrolyte excretion.

It is well known that Leonardo da Vinci made several drawings of the human male anatomy. The early drawings (before 1500) were incorrect in identifying the origin of semen, where he followed accepted teaching of his time. It is widely thought that he did not correct this mistake, a view that is reflected in several biographies. In fact, he made a later drawing (after 1500) in which the description of the anatomy is remarkably accurate and must have been based on careful dissection. In addition to highlighting this fact, acknowledged previously in only one other source, this article reviews the background to Leonardo's knowledge of the relevant anatomy. PMID:27494016

Intraoperative tracking of laparoscopic instruments is a prerequisite to realize further assistance functions. Since endoscopic images are always available, this sensor input can be used to localize the instruments without special devices or robot kinematics. In this paper, we present an image-based markerless 3D tracking of different da Vinci instruments in near real-time without an explicit model. The method is based on different visual cues to segment the instrument tip, calculates a tip point and uses a multiple object particle filter for tracking. The accuracy and robustness is evaluated with in vivo data.

A novel pipeline digital-to-analog converter configuration, based on switched-capacitor techniques, is described. An n-bit D/A conversion can be implemented by cascading n + 1 unit cells. The device count of the circuit increases linearly, not exponentially, with the conversion accuracy. The new configuration can be pipelined. Hence, the conversion rate can be increased without requiring a higher clock rate. An experimental 10-bit DAC prototype has been fabricated using a 3-micron CMOS process. The results show that high-speed, high-accuracy, and low-power operation can be achieved without special process or postprocess trimming.

The crystal structure of the C-terminal domain of a putative U32 peptidase from G. thermoleovorans is reported; it is one of the most tightly packed protein structures reported to date. While small organic molecules generally crystallize forming tightly packed lattices with little solvent content, proteins form air-sensitive high-solvent-content crystals. Here, the crystallization and full structure analysis of a novel recombinant 10 kDa protein corresponding to the C-terminal domain of a putative U32 peptidase are reported. The orthorhombic crystal contained only 24.5% solvent and is therefore among the most tightly packed protein lattices ever reported.

In the drawing of coitus by Leonardo da Vinci are pictured the contemporary hypotheses regarding this act. The authors analyze the mamillaruteral connection depicted by the artist and grow up to believe that this is a hypothetical kiveris vena, female vein described by Anatomist Master Nicolai Physicus from the Salerno School. The Hebrew roots were found in the name. The connection is described also by Mondino in The Anathomia. The same connection can be found in the picture of the pregnant woman in Fasciculus Medicinæ by Johannes De Ketham.

It is well known that Leonardo da Vinci made several drawings of the human male anatomy. The early drawings (before 1500) were incorrect in identifying the origin of semen, where he followed accepted teaching of his time. It is widely thought that he did not correct this mistake, a view that is reflected in several biographies. In fact, he made a later drawing (after 1500) in which the description of the anatomy is remarkably accurate and must have been based on careful dissection. In addition to highlighting this fact, acknowledged previously in only one other source, this article reviews the background to Leonardo's knowledge of the relevant anatomy.

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

A serine protease termed Da-36 was isolated from crude venom of Deinagkistrodon acutus. The enzyme was a single chain protein with an apparent molecular weight of 36,000 on SDS-PAGE with an isoelectric point of 6.59. Da-36 could clot human plasma by cleaving the Aα, Bβ and γ chains of fibrinogen and also exhibited arginine esterase activity. The proteolytic activity of Da-36 toward TAME was strongly inhibited by PMSF and moderately affected by benzamidine and aprotinin, indicating that it was a serine protease. Meanwhile, Da-36 showed stability with wide temperature (20-50 °C) and pH value ranges (pH 6-10). Divalent metal ions of Ca(2+), Mg(2+), and Mn(2+) had no effects but Zn(2+) and Cu(2+) inhibited the arginine esterase activity of Da-36. Total DNA was extracted directly from the lyophilized crude venom and the gene (5.5 kbp) coding for Da-36 had been successfully cloned. Sequence analysis revealed that the Da-36 gene contained five exons and four introns. The mature Da-36 was encoded by four separate exons. The deduced mature amino acid sequence of Da-36 was in good agreement with the determined N-terminal sequence of the purified protein and shared high homology with other serine proteases isolated from different snake venoms. Blast search using amino acid sequence of Da-36 against public database revealed that Da-36 showed a maximal identity of 90% with both Dav-X (Swiss-Prot: Q9I8W9.1) and thrombin-like protein 1 (GenBank: AAW56608.1) from the same snake species, indicating that Da-36 is a novel serine protease.

dA6m DNA immunoprecipitation followed by deep sequencing (DIP-Seq) is a key tool in identifying and studying the genome-wide distribution of N6-methyldeoxyadenosine (dA6m). The precise function of this novel DNA modification remains to be fully elucidated, but it is known to be absent from transcriptional start sites and excluded from exons, suggesting a role in transcriptional regulation (Koziol et al., 2015). Importantly, its existence suggests that DNA might be more diverse than previously believed, as further DNA modifications might exist in eukaryotic DNA (Koziol et al., 2015). This protocol describes the method to perform dA6m DNA immunoprecipitation (DIP), as was applied to characterize the first dA6m methylome analysis in higher eukaryotes (Koziol et al., 2015). In this protocol, we describe how genomic DNA is isolated, fragmented and then DNA containing dA6m is pulled down with an antibody that recognizes dA6m in genomic DNA. After subsequent washes, DNA fragments that do not contain dA6m are eliminated, and the dA6m containing fragments are eluted from the antibody in order to be processed further for subsequent analyses. Background This protocol was developed in order to identify regions in the genome that contain dA6m. It can be used to detect dA6m in different genomes. As a guideline, this protocol was established from existing approaches used to detect adenosine methylation in RNA (Dominissini et al., 2013). We developed this protocol and adapted it for the detection of dA6m in DNA, rather than detecting adenosine methylation RNA. This was required, as no protocol was available at that time to allow the genome-wide identification of dA6m in eukaryotic DNA. PMID:28180135

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction.

A rabbit antiserum to the 15-kDa acetylcholinesterase toxin neutralised the lethal effect of the 15-kDa toxin of Aeromonas hydrophila when injected into trout. However, immunisation of fish with the 15-kDa toxoid failed to induce an antibody response, and a higher molecular mass form of this toxin was purified from the extracellular products with the aim of inducing an immune response in fish. The optimal conditions for production of extracellular products by A. hydrophila strain B32 were studied to increase the concentration of this protoxin. The extracellular products were fractionated by molecular exclusion chromatography to yield a purified protoxin with an estimated molecular mass of 45 kDa by SDS-PAGE and which gave a positive reaction in Western blotting with the rabbit anti-15-kDa toxin serum. Since the 45-kDa protoxin showed lower specific acetylcholinesterase activity than the active 15-kDa toxin, the behaviour of the active site was studied using specific inhibitors. This 45-kDa protoxin was 13.3-fold less toxic than the 15-kDa toxin and induced antibody production in fish.

Previously we reported that PGBx, a prostaglandin oligomer with anti-inflammatory activity, inhibited 14 kDa phospholipase A2 (PLA2) activity and blocked arachidonic acid mobilization in prelabeled human neutrophils (Biochim. Biophys. Acta 1006:272-277, 278-286, 1989) This study describes a new inhibitor of phospholipase A2, PX-52, that also blocks agonist induced arachidonic acid mobilization in prelabeled cells. PX-52, a fatty acid polymer, inhibited hydrolysis of 14C-oleate labeled E.coli by a variety of 14 kDa PLA2s including human PMN, sperm, synovial fluid and disc, as well as porcine pancreas, N. naja, and bee venom in a dose-dependent manner with IC50s ranging from 1.0-3.7 uM. Inhibition of activity was comparable at different Ca2+ concentrations, but was relieved by increasing substrate concentration or by methylation of PX-52. Hydrolysis of [14C]-arachidonyl phosphatidylcholine by 85 kDa, cytosolic PLA2 from U937 cells was similarly inhibited by PX-52, the IC50 = 5 uM. Arachidonic acid mobilization induced by A23187 in prelabeled human PMNs was blocked by PX-52; IC50 = 10-15 uM while concentrations of up to 80 uM oleate had no effect. These results demonstrate that PX-52 inhibits the in vitro activity of secretory and cytosolic PLA2s and agonist-induced arachidonic acid release from human cells. Given its ability to block the arachidonic acid cascade, PX-52 may be useful in the control of inflammation.

As part of a multiwavelength study of the unusual radio supernova remnant DA 495, we present observations made with the Chandra X-ray Observatory. Imaging and spectroscopic analysis confirms the previously detected X-ray source at the heart of the annular radio nebula, establishing the radiative properties of two key emission components: a soft unresolved source with a blackbody temperature of 1 MK consistent with a neutron star, surrounded by a nontherma1 nebula 40" in diameter exhibiting a power-law spectrum with photon index Gamma = 1.63, typical of a pulsar wind nebula. Morphologically, the nebula appears to be slightly extended along a direction, in projection on the sky, previously demonstrated to be of significance in radio and ASCA observations; we argue that this represents the orientation of the pulsar spin axis. At smaller scales, a narrow X-ray feature is seen extending out 5" from the point source, but energetic arguments suggest that it is not the resolved termination shock of the pulsar wind against the ambient medium. Finally, we argue based on synchrotron lifetimes in the nebular magnetic field that DA 495 represents the first example of a pulsar wind nebula in which electromagnetic flux makes up a significant part, together with particle flux, of the neutron star's wind.

We have calibrated four major ground-based photometric systems with respect to the Hubble Space Telescope (HST) absolute flux scale, which is defined by Vega and four fundamental DA white dwarfs. These photometric systems include the Johnson-Kron-Cousins UBVRI, the Strömgren uvby filters, the Two Micron All Sky Survey JHKs, and the Sloan Digital Sky Survey ugriz filters. Synthetic magnitudes are calculated from model white dwarf spectra folded through the published filter response functions; these magnitudes in turn are absolutely calibrated with respect to the HST flux scale. Effective zero-magnitude fluxes and zero-point offsets of each system are determined. In order to verify the external observational consistency, as well as to demonstrate the applicability of these definitions, the synthetic magnitudes are compared with the respective observed magnitudes of larger sets of DA white dwarfs that have well-determined effective temperatures and surface gravities and span a wide range in both of these parameters.

Studies were done investigating the effect of the synaptic concentration of the transmitter DA, modified by changes in the frequency of electrical field stimulation and by the DA uptake inhibitor nomifensine, on the modulation of /sup 3/H-DA release by D-2 DA autoreceptors and by melatonin receptor sites. At lower synaptic concentrations of the transmitter dopamine, D-2 DA receptor agonists were more potent, while antagonists were more potent when the synaptic concentration of transmitter was higher. The potency of melatonin to inhibit DA release was not altered by the frequency of field stimulation of by frequency-dependent changes in the synaptic concentration of the transmitter.

Background The Mycobacterium tuberculosis 19-kDa lipoprotein has been reported to stimulate both T and B cell responses as well as induce a number of Th1 cytokines. In order to evaluate the Mycobacterium avium subsp. paratuberculosis (M. avium subsp. paratuberculosis) 19-kDa lipoprotein as an immunomodulator in cattle with Johne's disease, the gene encoding the 19-kDa protein (MAP0261c) was analyzed. Results MAP0261c is conserved in mycobacteria, showing a 95% amino acid identity in M. avium subspecies avium, 84% in M. intracellulare and 76% in M. bovis and M. tuberculosis. MAP0261c was cloned, expressed, and purified as a fusion protein with the maltose-binding protein (MBP-19 kDa) in Escherichia coli. IFN-γ production was measured from 21 naturally infected and 9 control cattle after peripheral blood mononuclear cells (PBMCs) were stimulated with a whole cell lysate (WCL) of M. avium subsp. paratuberculosis or the recombinant MBP-19 kDa. Overall, the mean response to MBP-19 kDa was not as strong as the mean response to the WCL. By comparison, cells from control, non-infected cattle did not produce IFN-γ after stimulation with either WCL or MBP-19 kDa. To assess the humoral immune response to the 19-kDa protein, sera from cattle with clinical Johne's disease were used in immunoblot analysis. Reactivity to MBP-19 kDa protein, but not MBP alone, was observed in 9 of 14 infected cattle. Antibodies to the 19-kDa protein were not observed in 8 of 9 control cows. Conclusions Collectively, these results demonstrate that while the 19-kDa protein from M. avium subsp. paratuberculosis stimulates a humoral immune response and weak IFN-γ production in infected cattle, the elicited responses are not strong enough to be used in a sensitive diagnostic assay. PMID:15663791

Neuronal loss is a major neuropathological hallmark of Alzheimer's disease (AD). The associations between soluble Aβ oligomers and cellular components cause this neurotoxicity. The 37 kDa/67 kDa laminin receptor (LRP/LR) has recently been implicated in Aβ pathogenesis. In this study the mechanism underlying the pathological role of LRP/LR was elucidated. Försters Resonance Energy Transfer (FRET) revealed that LRP/LR and Aβ form a biologically relevant interaction. The ability of LRP/LR to form stable associations with endogenously shed Aβ was confirmed by pull down assays and Aβ-ELISAs. Antibody blockade of this association significantly lowered Aβ42 induced apoptosis. Furthermore, antibody blockade and shRNA mediated downregulation of LRP/LR significantly hampered Aβ42 internalization. These results suggest that LRP/LR is a receptor for Aβ42 internalization, mediating its endocytosis and contributing to the cytotoxicity of the neuropeptide by facilitating intra-cellular Aβ42 accumulation. These findings recommend anti-LRP/LR specific antibodies and shRNAs as potential therapeutic tools for AD treatment. PMID:24990253

Understanding how dopamine (DA) phenotypes are acquired in midbrain DA (mDA) neuron development is important for bioassays and cell replacement therapy for mDA neuron-associated disorders. Here, we demonstrate a feed-forward mechanism of mDA neuron development involving Nurr1 and Foxa2. Nurr1 acts as a transcription factor for DA phenotype gene expression. However, Nurr1-mediated DA gene expression was inactivated by forming a protein complex with CoREST, and then recruiting histone deacetylase 1 (Hdac1), an enzyme catalyzing histone deacetylation, to DA gene promoters. Co-expression of Nurr1 and Foxa2 was established in mDA neuron precursor cells by a positive cross-regulatory loop. In the presence of Foxa2, the Nurr1-CoREST interaction was diminished (by competitive formation of the Nurr1-Foxa2 activator complex), and CoREST-Hdac1 proteins were less enriched in DA gene promoters. Consequently, histone 3 acetylation (H3Ac), which is responsible for open chromatin structures, was strikingly increased at DA phenotype gene promoters. These data establish the interplay of Nurr1 and Foxa2 as the crucial determinant for DA phenotype acquisition during mDA neuron development.

A syntactic-semantic investigation of subjunctive and indicative "da"-complements in Serbian is conducted in this project. After a careful comparison of Serbian sentence constructions with "da"-complements to the equivalent sentence structures in languages of the Balkans as well as other Slavic languages, it is clearly…

Background/Aims Acute gastric injury by alcohol or indomethacin has been reported to be prevented by DA-9601, an extract of the herb Artemisia asiatica. Ghrelin, an endogenously produced gastrointestinal peptide hormone, has also been demonstrated to play a role in gastric mucosal defense. The aim of this study was to investigate the effects of DA-9601 on ghrelin in an acute gastric injury model induced by alcohol or indomethacin. Methods A total of 140 Sprague-Dawley rats were divided into two groups, a placebo group and a DA-9601-pretreated group. Thirty minutes later, half of the rats in each group received ethanol injury and the other half received indomethacin injury. Levels of serum ghrelin and gastric mucosal ghrelin mRNA were measured by ELISA and RT-PCR, respectively. Results Immediately after ethanol administration, ghrelin increased in both groups pretreated with DA-9601 and placebo. However, the increase occurred more rapidly and was higher in the DA-9601-pretreated rats than in the controls that did not receive DA-9601-pretreatment. Similarly, from 30 minutes to 2 hours after indomethacin administration, the DA-9601-pretreated rats showed a significant increase in serum and gastric mucosal ghrelin concentrations, whereas placebo-pretreated rats showed only a mild increase. Conclusions DA-9601 potentiates the endogenous production and secretion of ghrelin in acute gastric injury models induced by ethanol or indomethacin. PMID:21461072

"A Creative Approach to the Common Core Standards: The Da Vinci Curriculum" challenges educators to design programs that boldly embrace the Common Core State Standards by imaginatively drawing from the genius of great men and women such as Leonardo da Vinci. A central figure in the High Renaissance, Leonardo made extraordinary contributions as a…

The history of veterinary medicine is closely tied to the development of human medicine. Evidence of animal medicine has been found in ancient civilizations, such as those of the Hindu, Babylonians, Hebrews, Arabs, Greeks, and Romans. Ancient Indian literature in the form of the holy Vĕda, Purăna, Brăhmaņa, epics, etc. is flooded with information on animal care. The Purăņa are ancient scriptures discuss varied topics like devotion to God and his various aspects, traditional sciences like Ayurvĕda, Jyŏtişa (Astrology), cosmology, concepts like dharma, karma, reincarnation and many others. The treatment of animal diseases using Ayurvedic medicine has been mentioned in Garudapurăna, Agnipurăņa, Atri-samhită, Matsyapurăņa and many other texts. The Garudapurăņa is one of the important Săttvika purăna, the subject matter is divided into two parts, viz. Pŭrvakhaņda (first part) and an Uttarakhaņda (subsequent part). Gavăyurvĕda, Gajăyurvĕda narrated briefly and Aśvăyurvĕda described detailly in Pŭrvakhaņda.

... 32 National Defense 3 2010-07-01 2010-07-01 true Power of Attorney (DA Form 4881-4-R) F Appendix F to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY SUPPLIES AND EQUIPMENT LOAN OF ARMY MATERIEL Pt. 623, App. F Appendix F to Part 623—Power of Attorney (DA Form...

... 32 National Defense 3 2011-07-01 2009-07-01 true Power of Attorney (DA Form 4881-4-R) F Appendix F to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY SUPPLIES AND EQUIPMENT LOAN OF ARMY MATERIEL Pt. 623, App. F Appendix F to Part 623—Power of Attorney (DA Form...

Insulin-receptor tyrosine kinase can phosphorylate a variety of artificial substrates in vitro. Its physiological substrate(s), however, remains unknown. In the present study, we show that immobilized insulin receptors phosphorylate tyrosine residues of two cytosolic proteins of 50 kDa and 35 kDa in rat liver. Phosphorylation of these two proteins required Mn2+- or Mg2+-ATP as the phosphate donor. Phosphorylation was time- and temperature-dependent. Furthermore, the rate of phosphorylation of the two proteins was related to the autophosphorylated state of the insulin receptor. The pI of the phosphorylated 50 kDa and 35 kDa proteins was 5.4 and 5.6 respectively. These proteins were present in low abundance. They were not related to each other, nor to the insulin receptor, as demonstrated by in-gel proteolytic digestion and by immunoprecipitation using antibodies produced against them. They were specific substrates for the insulin receptor kinase, since they were not phosphorylated by epidermal-growth-factor-receptor kinase. These observations suggest that the 50 kDa and 35 kDa cytosolic proteins may be endogenous substrates for the insulin-receptor kinase. Images Fig. 1. Fig. 2. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:2829823

Genus specific antigenicity of the 10 kDa protein in cyst fluid (CF) of Taenia solium metacestodes was demonstrated by comparative immunoblot analysis. When CFs from taeniid metacestodes of T. saginata, T. solium, T. taeniaeformis and T. crassiceps were probed with specific monoclonal antibody (mAb) raised against 150 kDa protein of T. solium metacestodes, specific antibody reactions were observed in 7 and 10 kDa proteins of T. solium and in 7/8 kDa of T. saginata, T. taeniaeformis and T. crassiceps. The mAb did not react with any protein in hydatid fluid of Echinococcus granulosus and E. multilocularis. This result revealed that the 10 kDa peptide of T. solium metacestodes and its equivalent proteins of different Taenia metacestodes are genus specific antigens that are shared among different Taenia species.

A pot experiment was carried out to study the effect of growth-promoting hormone diethyl aminoethyl hexanoate (DA-6) on Cd phytoextraction and detoxification in ryegrass. Foliar spray of DA-6 significantly enhanced Cd extraction efficiency (P<0.05), with 1 μM DA-6 the most effective. At the subcellular level, 43-53% of Cd was soluble fraction and 23-46% in cell wall, and 9-25% in organelles. Chemical speciation analysis showed that 52.7-58.5% of Cd was NaCl extractable, 12.1-22.7% ethanol extractable, followed by other fractions. DA-6 alleviated metal toxicity by fixing more Cd in cell wall and decreasing Cd migration in plant. In conclusion, ryegrass tolerates Cd by cell wall compartmentalization along with protein and organic acids combination, and the treatment of 1 μM DA-6 appears to be optimal for enhancing the remediation efficiency of ryegrass for Cd contaminated soil.

Motilitone(®) (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments.

Motilitone® (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments. PMID:24265862

Extensive observations from the Kepler spacecraft have recently revealed a new outburst phenomenon operating in cool pulsating DA (hydrogen atmosphere) white dwarfs (DAVs). With the introduction of two new outbursting DAVs from K2 Fields 7 (EPIC 229228364) and 8 (EPIC 220453225) in these proceedings, we presently know of six total members of this class of object. We present the observational commonalities of the outbursting DAVs: (1) outbursts that increase the mean stellar flux by up to ≍15%, last many hours, and recur irregularly on timescales of days; (2) effective temperatures that locate them near the cool edge of the DAV instability strip; and (3) rich pulsation spectra with modes that are observed to wander in amplitude/frequency.

We purified to apparent homogeneity a human urinary glycoprotein of 92 kDa (HGP.92) that, administered intravenously at 250 micrograms/kg, fully protected mice against a lethal inoculum of Listeria monocytogenes. Since HGP.92 protected scid mice, which lack B and T lymphocytes, this increased resistance to Listeria did not appear to be lymphocyte mediated. Furthermore, inflammatory macrophages incubated with 6 nM HGP.92 inhibited the growth of Lewis carcinoma cells in vitro. These two activities appeared to depend on an oligosaccharide moiety, as they were lost after N-Glycanase treatment of HGP.92. Thus, the biological activity of HGP.92 was in some way related to a glycan moiety. Images PMID:8078887

An experiment on VLBI radar of the 2012 DA14 asteroid was carried out on February 15-16, 2011 at the time of its closest approach to the Earth. The research teams of Kharkov (Institute of Radio Astronomy of the National Academy of Sciences of Ukraine), Evpatoria (National Space Facilities Control and Test Center), Nizhny Novgorod (Radiophysical Research Institute), Bologna (Istituto di Radioastronomia (INAF)), and Ventspils (Ventspils International Radioastronomy Center) took part in the experiment. The asteroid was irradiated by the RT-70 planetary radar (Evpatoria) at a frequency of 5 GHz. The reflected signal was received using two 32-m radio telescopes in Medicina (Italy) and Irbene (Latvia) in radiointerferometric mode. The Doppler frequency shifts in bi-static radar mode and interference frequency in VLBI mode were measured. Accuracy of the VLBI radar method for determining the radial and angular velocities of the asteroid were estimated.

The human race has always contemplated the question of the anatomical location of the soul. During the Renaissance the controversy crystallized into those individuals who supported the heart ("cardiocentric soul") and others who supported the brain ("cephalocentric soul") as the abode for this elusive entity. Leonardo da Vinci (1452-1519) joined a long list of other explorers in the "search for the soul." The method he used to resolve this anatomical problem involved the accumulation of information from ancient and contemporary sources, careful notetaking, discussions with acknowledged experts, and his own personal search for the truth. Leonardo used a myriad of innovative methods acquired from his knowledge of painting, sculpture, and architecture to define more clearly the site of the "senso comune"--the soul. In this review the author examines the sources of this ancient question, the knowledge base tapped by Leonardo for his personal search for the soul, and the views of key individuals who followed him.

Leonardo da Vinci's Manuscript D consists of five double pages sheets, which, folded in two, comprise ten folios. This document, in the old Tuscan dialect and mirror writing, reveals the ideas of Leonardo on the anatomy of the eye in relation to the formation of images and visual perception. Leonardo explains in particular the behavior of the rays in the eye in terms of refraction and reflection, and is very mechanistic in his conception of the eye and of the visual process. The most significant innovations found in these folios are the concept of the eye as a camera obscura and the intersection of light rays in the interior of the eye. His texts nevertheless show hesitation, doubts and a troubled confusion, reflecting the ideas and uncertainties of his era. He did not share his results in his lifetime, despite both printing and etching being readily available to him.

The aim of this article is to reflect on the relationship between art and science so far as it concerns a symposium on neurosciences. We undertake a historical overview of that relationship, paying particular attention to the sui generis case of Leonardo da Vinci, who very often is regarded as the man who worked on art and science with equal ease. We then explain why his idea of merging these two forms of knowledge failed, considering the clear-cut distinction between art and science in his time. With this clarification, we explore the matter today. We look at Raphael's The Transfiguration, in which the representation of the possessed boy is seen by neuroscientists as indicative of an epileptic seizure. We also look at the ideas of neuroscientists Semir Zeki and Vilayanur Ramachandran, who study particular aspects of brain function and suggest a new merging of art and science.

Objective: To define the learning curve for daVinci-assisted laparoscopic radical prostatectomy (DLP) at our institution. Methods: The data from 170 patients who underwent DLP between August 2002 and December 2004 by a single surgeon (MTG) were reviewed. Operative time, hemoglobin decrease, conversion to open procedure, positive margin rates, complications, length of stay (LOS), length of catheterization, continence, and erectile function were analyzed. Results: Hemoglobin decrease (p=0.11), positive margin rates (p=0.80), and early urinary continence (p=0.17) did not significantly correlate with surgical experience. A trend towards lower complications (p=0.07) and an earlier return of erectile function (p=0.09) was noted with increased experience with DLP. Operative time, hospital stay, catheterization time, and open conversion showed significant association with patient sequence. Median operative time for the first 60 and the last 110 patients was 323.5 and 239.5 minutes (p=<0.0001), respectively. Median LOS for the aforementioned groups was 53 and 51 hours (p=0.009). Length of catheterization declined significantly between the first 60 and the remaining 110 patients, 14 as compared to 11.5 days (p=<0.0001). Eight open conversions occurred, six were in the first 30 patients (p=0.03). Conclusion: As an indicator of the learning curve, the operative time in our series showed no correlation with sequence after the 60 th patient. Thus, despite the advantages of robotics, the learning curve to efficient performance of daVinciassisted laparoscopic radical prostatectomy is long. Oncological and functional outcomes should not be affected during the learning curve.

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.Neuropsychopharmacology advance online

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity.

AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats. METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is a promising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increased mucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis. PMID:16437712

Background/Aims Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. Methods The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. Results DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. Conclusions DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD. PMID:26932898

Low-bandgap near-infrared polymers are usually synthesized using the common donor-acceptor (D-A) approach. However, recently polymer chemists are introducing more complex chemical concepts for better fine tuning of their optoelectronic properties. Usually these studies are limited to one or two polymer examples in each case study so far, though. In this study, the dependence of optoelectronic and macroscopic (device performance) properties in a series of six new D-A1 -D-A2 low bandgap semiconducting polymers is reported for the first time. Correlation between the chemical structure of single-component polymer films and their optoelectronic properties has been achieved in terms of absorption maxima, optical bandgap, ionization potential, and electron affinity. Preliminary organic photovoltaic results based on blends of the D-A1 -D-A2 polymers as the electron donor mixed with the fullerene derivative [6,6]-phenyl-C71 -butyric acid methyl ester demonstrate power conversion efficiencies close to 4% with short-circuit current densities (J sc ) of around 11 mA cm(-2) , high fill factors up to 0.70, and high open-circuit voltages (V oc s) of 0.70 V. All the devices are fabricated in an inverted architecture with the photoactive layer processed in air with doctor blade technique, showing the compatibility with roll-to-roll large-scale manufacturing processes.

The hunt for an effective vaccine against malaria still continues. Several new target antigens as candidates for vaccine design are being explored and tested for their efficacy. In the present study the sera from mice immunized with 24,000 x g fraction of Plasmodium berghei has been used to identify highly immunogenic blood stage antigens. The protective antibodies present in immune sera were covalently immobilized on CNBr activated sepharose 4B and used for affinity chromatography purification of antigens present in blood stages of P. berghei. Two polypeptides of 66 and 43 kDa molecular weights proved to be highly immunogenic. They exhibited a strong humoral immune response in mice as evident by high titres in ELISA and IFA. Protective immunity by these two antigens was apparent by in vivo and in vitro studies. These two proteins could further be analysed and used as antigens in malaria vaccine design.

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Legumes, including soybeans ( Glycine max ), are deficient in sulfur-containing amino acids, which are required for the optimal growth of monogastric animals. This deficiency can be overcome by expressing heterologous proteins rich in sulfur-containing amino acids in soybean seeds. A maize 27 kDa γ-zein, a cysteine-rich protein, has been successfully expressed in several crops including soybean, barley, and alfalfa with the intent to biofortify these crops for animal feed. Previous work has shown that the maize 27 kDa zein can withstand digestion by pepsin and elicit an immunogenic response in young pigs. By use of sera from patients who tested positive by ImmunoCAP assay for elevated IgE to maize proteins, specific IgE binding to the 27 kDa γ-zein is demonstrated. Bioinformatic analysis using the full-length and 80 amino acid sliding window FASTA searches identified significant sequence homology of the 27 kDa γ-zein with several known allergens. Immunoblot analysis using human serum that cross-reacts with maize seed proteins also revealed specific IgE-binding to the 27 kDa γ-zein in soybean seed protein extracts containing the 27 kDa zein. This study demonstrates for the first time the allergenicity potential of the 27 kDa γ-zein and the potential that this protein has to limit livestock performance when used in soybeans that serve as a biofortified feed supplement.

E proteins are a special class of basic helix-loop-helix (bHLH) proteins that heterodimerize with many bHLH activators to regulate developmental decisions, such as myogenesis and neurogenesis. Daughterless (Da) is the sole E protein in Drosophila and is ubiquitously expressed. We have characterized two transcription activation domains (TADs) in Da, called activation domain 1 (AD1) and loop-helix (LH), and have evaluated their roles in promoting peripheral neurogenesis. In this context, Da heterodimerizes with proneural proteins, such as Scute (Sc), which is dynamically expressed and also contributes a TAD. We found that either one of the Da TADs in the Da/Sc complex is sufficient to promote neurogenesis, whereas the Sc TAD is incapable of doing so. Besides its transcriptional activation role, the Da AD1 domain serves as an interaction platform for E(spl) proteins, bHLH-Orange family repressors which antagonize Da/Sc function. We show that the E(spl) Orange domain is needed for this interaction and strongly contributes to the antiproneural activity of E(spl) proteins. We present a mechanistic model on the interplay of these bHLH factors in the context of neural fate assignment.

Granulysin, a cationic protein expressed by human natural killer cells and cytotoxic T lymphocytes, is a mediator for drug-induced Stevens-Johnson syndrome and graft-versus-host disease. Some 15 kDa granulysin are processed into 9 kDa forms and sequestered in cytolytic granules, while others are constitutively secreted into body fluids. Both 9 and 15 kDa granulysin have been shown to be a serum marker for cell-mediated immunity. Furthermore, 15 kDa is able to activate monocyte differentiation. However, its antimicrobial properties have not been clearly addressed. Here, we report a novel method to prepare both the soluble 9 and 15 kDa granulysin and show that the 15 kDa form is more effective than the 9 kDa form in exerting specific antimicrobial activity against Pseudomonas aeruginosa within a range of few micromolars. We also show that the 15 kDa granulysin is able to hyperpolarize the membrane potential and increase membrane permeability of treated bacteria. Interestingly, the bactericidal activity and membrane permeability of the granulysins were markedly reduced at lower pH (pH 5.4) as a result of probable increase in hydrophobicity of the granulysins. Additionally, we’ve also shown the granulysin to inhibit biofilm formation by P. aeruginosa. These results suggest that the 15 kDa granulysin exhibits a novel mechanism in bacteria killing in a way that’s different from most antimicrobial peptides. Our novel granulysin preparation methodology will be useful for further study of action mechanisms of other antimicrobial, cytotoxic and immunomodulating properties in granulysin-mediated diseases. PMID:27276051

The perfluorochemical emulsion Fluosol-DA plus carbogen breathing has been shown to increase the effectiveness of radiation therapy in preclinical solid tumors when the emulsion was administered by i.v. bolus injection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. The authors hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly. In the present study, the [alpha]/[beta] agonist ephedrine, the Ca[sup 2+] channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested. Ephedrine administration resulted in a decrease in the radiation plus Fluosol-DA [+-] carbogen antitumor effects in both the Lewis lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine administration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both emulsion was given rapidly. Even with flunarizine administration Fluosol-DA delivered slowly was less effective than when the emulsion was given rapidly. Flunarizine with Fluosol-DA infused i.v. over 30 min followed by carbogen breathing prior to and during radiation therapy resulted in a 1.7-1.6-fold increase in response compared with 2.4-2.2-fold with Fluosol-DA administered by injection i.v. and carbogen breathing prior to and during radiation therapy using growth delay of the Lewis lung carcinoma. The effects of nitroprusside were complex. This drug had considerably more effect at 10 Gy than at higher radiation doses. These studies suggest that Fluosol-DA given by i.v. injection may increase tumor perfusion and that a drug like flunarizine may be beneficial if the Fluosol-DA is administered slowly followed by carbogen breathing and radiation therapy. 45 refs., 4 figs.

Influence of dietary protein deficiency on the pharmacokinetics of DA-8159 and one of its metabolites, DA-8164, was investigated after intravenous and oral administration of DA-8159 at a dose of 30 mg kg(-1) to male Sprague-Dawley rats allowed free access to a 23% (control) or 5% (protein-calorie malnutrition, PCM) casein diet for 4 weeks. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values of DA-8164 were significantly smaller after both intravenous (87.0 vs 162 microg min mL(-1)) and oral (144 vs 319 microg min mL(-1)) administration of DA-8159 to PCM rats. This could be due to the decrease in CYP3A1/2 (50-60%) in the rats because DA-8164 was mainly formed via CYP3A1/2 in rats. This could be supported by significantly slower in-vitro CL(int) (2.04+/-0.646 vs 3.15+/-0.693 microL min(-1) (mg protein)(-1)) for the formation of DA-8164 in hepatic microsomal fraction of PCM rats. After intravenous administration of DA-8159, the AUC values of DA-8159 were not significantly different between the two groups of rats although the AUC of DA-8164 was significantly smaller in PCM rats, and this may be due to the minor metabolic pathway of DA-8164 in rats. However, after oral administration of DA-8159, the AUC of DA-8159 was significantly greater in PCM rats (194 vs 122 microg min mL(-1)). This was not due to enhanced absorption of DA-8159 from the gastrointestinal tract in the rats but may be due to a decreased intestinal first-pass effect of DA-8159 in the rats.

Background Protein histidine phosphatase (PHP) is an enzyme which removes phosphate groups from histidine residues. It was described for vertebrates in the year 2002. The recombinant human 16 kDa protein forms multimeric complexes in physiological buffer and in the gas phase. High-mass calibration in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has remained a problem due to the lack of suitable standards. Large proteins can hardly be freed of their substructural microheterogeneity by classical purification procedures so that their use as calibrants is limited. A small adduct-forming protein of validated quality is a valuable alternative for that purpose. Methodology/Principal Findings Three major PHP clusters of ∼113, 209 and >600 kDa were observed in gel filtration analysis. Re-chromatography of the monomer peak showed the same cluster distribution. The tendency to associate was detected also in MALDI-TOF MS measuring regular adducts up to 200 kDa. Conclusions/Significance PHP forms multimers consisting of up to more than 35 protein molecules. In MALDI-TOF MS it generates adduct ions every 16 kDa. The protein can be produced with high quality so that its use as calibration compound for high mass ranges above 100 kDa, where standards are difficult to obtain, is feasible. PMID:21876758

The classic myelin basic protein (MBP) splice isoforms range in nominal molecular mass from 14 to 21.5 kDa, and arise from the gene in the oligodendrocyte lineage (Golli) in maturing oligodendrocytes. The 18.5-kDa isoform that predominates in adult myelin adheres the cytosolic surfaces of oligodendrocyte membranes together, and forms a two-dimensional molecular sieve restricting protein diffusion into compact myelin. However, this protein has additional roles including cytoskeletal assembly and membrane extension, binding to SH3-domains, participation in Fyn-mediated signaling pathways, sequestration of phosphoinositides, and maintenance of calcium homeostasis. Of the diverse post-translational modifications of this isoform, phosphorylation is the most dynamic, and modulates 18.5-kDa MBP's protein-membrane and protein-protein interactions, indicative of a rich repertoire of functions. In developing and mature myelin, phosphorylation can result in microdomain or even nuclear targeting of the protein, supporting the conclusion that 18.5-kDa MBP has significant roles beyond membrane adhesion. The full-length, early-developmental 21.5-kDa splice isoform is predominantly karyophilic due to a non-traditional P-Y nuclear localization signal, with effects such as promotion of oligodendrocyte proliferation. We discuss in vitro and recent in vivo evidence for multifunctionality of these classic basic proteins of myelin, and argue for a systematic evaluation of the temporal and spatial distributions of these protein isoforms, and their modified variants, during oligodendrocyte differentiation.

The dust-ion-acoustic (DIA) as well as the dust-acoustic (DA) solitary waves (SWs) in an adiabatic dusty plasma are investigated by the pseudo-potential approach which is valid for arbitrary amplitude SWs. The role of the adiabaticity of electrons and ions in modifying the basic features (polarity, speed, amplitude and width) of arbitrary amplitude DIA and DA SWs are explicitly examined. It is found that the effects of the adiabaticity of electrons and ions significantly modify the basic features (polarity, speed, amplitude and width) of the DIA and DA SWs. The implications of our results in space and laboratory dusty plasmas are briefly discussed.

The PanDA (Production and Distributed Analysis) system plays a key role in the ATLAS distributed computing infrastructure. PanDA is the ATLAS workload management system for processing all Monte-Carlo (MC) simulation and data reprocessing jobs in addition to user and group analysis jobs. The PanDA Dynamic Data Placement (PD2P) system has been developed to cope with difficulties of data placement for ATLAS. We will describe the design of the new system, its performance during the past year of data taking, dramatic improvements it has brought about in the efficient use of storage and processing resources, and plans for the future.

We present daVinci Canvas: a telerobotic surgical system with integrated robot-assisted laparoscopic ultrasound capability. DaVinci Canvas consists of the integration of a rigid laparoscopic ultrasound probe with the daVinci robot, video tracking of ultrasound probe motions, endoscope and ultrasound calibration and registration, autonomous robot motions, and the display of registered 2D and 3D ultrasound images. Although we used laparoscopic liver cancer surgery as a focusing application, our broader aim was the development of a versatile system that would be useful for many procedures.

The PanDA (Production and Distributed Analysis) system plays a key role in the ATLAS distributed computing infrastructure. PanDA is the ATLAS workload management system for processing all Monte-Carlo (MC) simulation and data reprocessing jobs in addition to user and group analysis jobs. The PanDA Dynamic Data Placement (PD2P) system has been developed to cope with difficulties of data placement for ATLAS. We will describe the design of the new system, its performance during the past year of data taking, dramatic improvements it has brought about in the efficient use of storage and processing resources, and plans for the future.

Leonardo da Vinci (April 15, 1452 to May 2, 1519) was an Italian Renaissance architect, musician, anatomist, inventor, engineer, sculptor, geometer, and painter. It has been gleaned from the many available historical documents that da Vinci was a vegetarian who respected and loved animals, and that he suffered from right hemiparesis in the last 5 years of his life. A vegetarian diet has both positive and negative influences on the cerebrovascular system. In this report, a possible relation between a vegetarian diet and stroke is discussed from various perspectives as related to Leonardo da Vinci's stroke.

The Middle Pleistocene is a crucial time period for studying human evolution in Europe, because it marks the appearance of both fossil hominins ancestral to the later Neandertals and the Acheulean technology. Nevertheless, European sites containing well-dated human remains associated with an Acheulean toolkit remain scarce. The earliest European hominin crania associated with Acheulean handaxes are at the sites of Arago, Atapuerca Sima de los Huesos (SH), and Swanscombe, dating to 400–500 ka (Marine Isotope Stage 11–12). The Atapuerca (SH) fossils and the Swanscombe cranium belong to the Neandertal clade, whereas the Arago hominins have been attributed to an incipient stage of Neandertal evolution, to Homo heidelbergensis, or to a subspecies of Homo erectus. A recently discovered cranium (Aroeira 3) from the Gruta da Aroeira (Almonda karst system, Portugal) dating to 390–436 ka provides important evidence on the earliest European Acheulean-bearing hominins. This cranium is represented by most of the right half of a calvarium (with the exception of the missing occipital bone) and a fragmentary right maxilla preserving part of the nasal floor and two fragmentary molars. The combination of traits in the Aroeira 3 cranium augments the previously documented diversity in the European Middle Pleistocene fossil record. PMID:28289213

The Middle Pleistocene is a crucial time period for studying human evolution in Europe, because it marks the appearance of both fossil hominins ancestral to the later Neandertals and the Acheulean technology. Nevertheless, European sites containing well-dated human remains associated with an Acheulean toolkit remain scarce. The earliest European hominin crania associated with Acheulean handaxes are at the sites of Arago, Atapuerca Sima de los Huesos (SH), and Swanscombe, dating to 400-500 ka (Marine Isotope Stage 11-12). The Atapuerca (SH) fossils and the Swanscombe cranium belong to the Neandertal clade, whereas the Arago hominins have been attributed to an incipient stage of Neandertal evolution, to Homo heidelbergensis, or to a subspecies of Homo erectus A recently discovered cranium (Aroeira 3) from the Gruta da Aroeira (Almonda karst system, Portugal) dating to 390-436 ka provides important evidence on the earliest European Acheulean-bearing hominins. This cranium is represented by most of the right half of a calvarium (with the exception of the missing occipital bone) and a fragmentary right maxilla preserving part of the nasal floor and two fragmentary molars. The combination of traits in the Aroeira 3 cranium augments the previously documented diversity in the European Middle Pleistocene fossil record.

A total of {approx}640, 000 objects from the LAMOST pilot survey have been publicly released. In this work, we present a catalog of DA white dwarfs (DAWDs) from the entire pilot survey. We outline a new algorithm for the selection of white dwarfs (WDs) by fitting Sersic profiles to the Balmer H{beta}, H{gamma}, and H{delta} lines of the spectra, and calculating the equivalent width of the Ca II K line. Two thousand nine hundred sixty-four candidates are selected by constraining the fitting parameters and the equivalent width of the Ca II K line. All the spectra of candidates are visually inspected. We identify 230 DAWDs (59 of which are already included in the Villanova and SDSS WD catalogs), 20 of which are DAWDs with non-degenerate companions. In addition, 128 candidates are classified as DAWDs/subdwarfs, which means the classifications are ambiguous. The result is consistent with the expected DAWD number estimated based on the LEGUE target selection algorithm.

Leonardo da Vinci (1452-1519) enjoys a reputation as one of the most talented people of all time in the history of science and the arts. However, little attention has been given to his contributions to physiology. One of his main interests was engineering, and he was fascinated by structural problems and the flow patterns of liquids. He also produced a large number of ingenious designs for warfare and a variety of highly original flying machines. But of particular interest to us are his contributions to bioengineering and how he used his knowledge of basic physical principles to throw light on physiological function. For example, he produced new insights into the mechanics of breathing including the action of the ribs and diaphragm. He was the first person to understand the different roles of the internal and external intercostal muscles. He had novel ideas about the airways including the mode of airflow in them. He also worked on the cardiovascular system and had a special interest in the pulmonary circulation. But, interestingly, he was not able to completely divorce his views from those of Galen, in that although he could not see pores in the interventricular septum of the heart, one of his drawings included them. Leonardo was a talented anatomist who made many striking drawings of the human body. Finally, his reputation for many people is based on his paintings including the Mona Lisa that apparently attracts more viewers than any other painting in the world.

The aim of the present paper is to inform physicians about the work completed by nurses and professors of baccalaureat nurses in the framework of Leonardo da Vinci project, organised and sponsored by the European Union. The goal of the project was to increase the effectiveness of chief nurses throughout their further training programme in the field of management. The team of Szeged chose the human resource management, since in this field is possible to achieve the greatest improvement with the smallest financial investment. We measured the fluctuations and the absentees of the nurses, the changes in the degree of education, the nurse' and patient' satisfaction at the beginning and at the end of the period studied. Except the patient's satisfaction all the other parameters improved by the end of tested period. The project provided a unique possibility to compare the state of the Hungarian nursing with that of the countries belonging to the European Union, to exchange the experience and to learn some new methods. In the framework of this project a book of two volumes was prepared containing the suggestions of EU. This book is widely available in English and in French.

The atmospheres of very cool, hydrogen-rich white dwarfs (WDs) (T{sub eff} < 6000 K) are challenging to model because of the increased complexity of the equation of state, chemical equilibrium, and opacity sources in a low-temperature, weakly ionized dense gas. In particular, many models that assume relatively simple models for the broadening of atomic levels and mostly ideal gas physics overestimate the flux in the blue part of their spectra. A solution to this problem that has met with some success is that additional opacity at short wavelengths comes for the extreme broadening of the Lyman α line of atomic H by collisions primarily with H{sub 2}. For the purpose of validating this model more rigorously, we acquired Hubble Space Telescope STIS spectra of eight very cool WDs (five DA and three DC stars). Combined with their known parallaxes, BVRIJHK, and Spitzer IRAC photometry, we analyze their entire spectral energy distribution (from 0.24 to 9.3 μm) with a large grid of model atmospheres and synthetic spectra. We find that the red wing of the Lyman α line reproduces the rapidly decreasing near-UV flux of these very cool stars very well. We determine better constrained values of T{sub eff} and gravity as well as upper limits to the helium abundance in their atmospheres.

General description, textural, and compositional features of the polymict ureilite DaG 1066, recovered in 1999 in Libya, are provided. The meteorite contains various inclusions, among which almost pure forsterite and enstatite-bearing chondrules.

A confirmatory analysis was performed to validate the Questionnaire on the Health Staff's Perceptions Regarding Doutores da Alegria's Intervention, a 40-item instrument designed to assess pediatric staff's perceptions regarding the effects of Doutores da Alegria, a Brazilian hospital clowning professional organization. Eight dimensions were evaluated: the permanence of Doutores da Alegria's interventions; Doutores da Alegria's intrapersonal and interpersonal effects on their relation to health staff; themselves; staff-children; and staff-family relationships; as well as their effect on staff's cultural development; children's relation to their own disease; and families' attitude regarding their child's condition. In all, 567 health professionals from 13 Brazilian hospitals participated. The instrument's good psychometric features are acknowledged.

Most people when asked to name the most creative, innovative, and multidimensional people in history would agree that Leonardo da Vinci is either at the top or very close to the number one position on that list. Wouldn't it be nice to think like da Vinci? This article shares the seven unique principles of thinking that da Vinci used that enabled him to be the greatest painter, sculptor, architect, musician, mathematician, engineer, inventor, anatomist, geologist, cartographer, botanist, and writer of his (if not of all) time. This article will take you deep into the notebooks and codices of da Vinci, and suggest ways his ideas can be used by anyone in the healthcare profession to make them a better healthcare provider.

To study diagnostic epitopes within the Taenia solium 8 kDa antigen family, six overlapping synthetic peptides from an 8 kDa family member (Ts8B2) were synthesized and evaluated by ELISA and MABA with sera from patients with neurocysticercosis (NCC), from infected pigs and from rabbits immunized with recombinant Ts8B2 protein. The pre-immune rabbit sera and the Ts8B2 recombinant protein served as negative and positive controls, respectively. A similar analysis was done with the already described antigenic peptides from another member of the 8 kDa family, highly similar to Ts8B2, the CyDA antigen. Surprisingly, neither the Ts8B2 peptides nor the CyDA peptides were recognized by infected human and porcine sera. However, the entire Ts8B2 recombinant, as well as amino and carboxy-terminal halves were recognized by the positive serum samples. The observed lack of recognition of linear Ts8B2 peptides suggests that the principal serological response to the Ts8B2 family is focused on conformational epitopes in contrast to the previously observed antigenicity of the CyDA peptides. This differential antigenicity of 8 kDa family peptides could be related with parasite antigenic variability. The fact that rabbits experimentally immunized with Ts8B2 did make anti-peptide antibodies to peptides Ts8B2-6 and CyDA-6, located in the carboxy-terminal region demonstrated that the Ts8B2 peptides are not intrinsically non-immunogenic.

Transoral robotic surgery, performed with the da Vinci surgical system (da Vinci), is a surgical approach for benign and malignant lesions of the oral cavity and laryngopharynx. It provides several unique advantages, which include a 3-dimensional magnified view and ability to see and work around curves or angles. However, the current da Vinci surgical system does not provide haptic feedback. This is problematic because the potential risks specific to the transoral use of the da Vinci include tooth injury, mucosal laceration, ocular injury and mandibular fracture. To assess the potential for intraoperative injuries, we measured the load of the endoscope and the instrument of the da Vinci Si surgical system. We pressed the endoscope and instrument of the da Vinci Si against Load cell six times each and measured the dynamic load and the time-to-maximum load. We also struck the da Vinci Si endoscope and instrument against the Load cell six times each and measured the impact load. The maximum dynamic load was 7.27 ± 1.31 kg for the endoscope and 1.90 ± 0.72 for the instrument. The corresponding time-to-maximum loads were 1.72 ± 0.22 and 1.29 ± 0.34 s, but the impact loads were significantly lower than the dynamic load. It remains possible that a major load is exerted on adjacent structures by continuous contact with the endoscope and instrument of da Vinci Si. However, there is a minor delay in reaching the maximum load. Careful monitoring by an on-site assistant may, therefore, help prevent contiguous injury.

The da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2014 to facilitate minimally invasive surgery. Novel features are targeted towards facilitating complex multi-quadrant procedures, but data is scarce so far. Perioperative data of patients who underwent robotic general surgery with the da Vinci Xi system within the first 6 month after installation were collected and analyzed. The gastric bypass procedures performed with the da Vinci Xi Surgical System were compared to an equal amount of the last procedures with the da Vinci Si Surgical System. Thirty-one foregut (28 Roux-en-Y gastric bypasses), 6 colorectal procedures and 1 revisional biliary procedure were performed. The mean operating room (OR) time was 221.8 (±69.0) minutes for gastric bypasses and 306.5 (±48.8) for colorectal procedures with mean docking time of 9.4 (±3.8) minutes. The gastric bypass procedure was transitioned from a hybrid to a fully robotic approach. In comparison to the last 28 gastric bypass procedures performed with the da Vinci Si Surgical System, the OR time was comparable (226.9 versus 230.6 min, p = 0.8094), but the docking time significantly longer with the da Vinci Xi Surgical System (8.5 versus 6.1 min, p = 0.0415). All colorectal procedures were performed with a single robotic docking. No intraoperative and two postoperative complications occurred. The da Vinci Xi might facilitate single-setups of totally robotic gastric bypass and colorectal surgeries. However, further comparable research is needed to clearly determine the significance of this latest version of the da Vinci Surgical System.

Type XIV collagen is a newly described member of the fibril-associated collagens with interrupted triple helices (FACITs). Expression of this collagen has been localized to various embryonic tissues, suggesting that it has a functional role in development. All FACITs thus far described (types IX, XII, XIV, and XVI) contain a highly homologous carboxyl-terminal triple helical domain designated COL1. We have studied the capacity of various matrix metalloproteinases (interstitial collagenase, stromelysin, matrilysin, and 92-kDa gelatinase) to degrade the COL1 domain of collagen XIV. We found that only 92-kDa gelatinase cleaves COL1. Furthermore, digestion of whole native collagen XIV by the 92-kDa gelatinase indicates that this enzyme specifically attacks the carboxyl-terminal triple helix-containing region of the molecule. COL1 is cleaved by 92-kDa gelatinase at 30 degrees C, a full 5-6 degrees C below the melting temperature (Tm) of this domain; native collagen XIV is also degraded at 30 degrees C. In comparison to interstitial collagenase degradation of its physiologic native type I collagen substrate, the 92-kDa enzyme cleaved COL1 (XIV) with comparable catalytic efficacy. Interestingly, following thermal denaturation of the COL1 fragment, its susceptibility to 92-kDa gelatinase increases, but only to a degree that leaves it several orders of magnitude less sensitive to degradation than denatured collagens I and III. These data indicate that native COL1 and collagen XIV are readily and specifically cleaved by 92-kDa gelatinase. They also suggest a role for 92-kDa gelatinase activity in the structural tissue remodeling of the developing embryo.

We report on the status of the PAN-DA data acquisition system presented at the last Real Time Conference. Since that time, PAN-DA has been successfully used in the fixed target program at Fermilab. We also report on the plans and strategies for development of a new data acquisition system for the next generation of fixed target experiments at Fermilab. 10 refs., 3 figs.

EUV spectroscopy has shown that DA white dwarfs hotter than about 45,000 K may contain trace heavy elements, while those hotter than about 50,000 K almost always have significant abundances of trace heavy elements. One of our continuing challenges is to identify and determine the abundances of these trace constituents, and then to relate the observed abundance patterns to the present conditions and previous evolutionary histories of the hot DA white dwarfs.

Cutaneous leishmaniasis (CL) in the state of Rio de Janeiro is sporadic and can be characterised as a peridomestic transmission that occurs in modified natural environments. The aim of this work was to study the fauna and ecological characteristics of sandflies in an environmentally protected area (the State Park of Serra da Tiririca) within the remnants of the Atlantic Forest in the municipalities of Niterói and Maricá and their possible relationship with leishmaniasis. Captures were performed using light traps during the night once a month for one year in both sylvatic environments and areas surrounding homes near the park. A total of 1,037 sandflies were captured, belonging to nine genera and 12 species: Evandromyia tupynambai (34.1%), Migonemyia migonei (20.6%), Brumptomyia cunhai (13.8%), Micropygomyia schreiberi (9.7%), Psathyromyia lanei (6.5%), Brumptomyia nitzulescui (5.7%), Evandromyia edwardsi (5.4%), Nyssomyia intermedia (2.8%), Evandromyia cortelezzii (0.6%), Pintomyia bianchigalatiae (0.5%), Lutzomyia longipalpis (0.2%) and Sciopemyia microps (0.1%). Both Mg. migonei and Ny. intermedia may be acting as vectors of CL in this area. PMID:24141956

Cutaneous leishmaniasis (CL) in the state of Rio de Janeiro is sporadic and can be characterised as a peridomestic transmission that occurs in modified natural environments. The aim of this work was to study the fauna and ecological characteristics of sandflies in an environmentally protected area (the State Park of Serra da Tiririca) within the remnants of the Atlantic Forest in the municipalities of Niterói and Maricá and their possible relationship with leishmaniasis. Captures were performed using light traps during the night once a month for one year in both sylvatic environments and areas surrounding homes near the park. A total of 1,037 sandflies were captured, belonging to nine genera and 12 species: Evandromyia tupynambai (34.1%), Migonemyia migonei (20.6%), Brumptomyia cunhai (13.8%), Micropygomyia schreiberi (9.7%), Psathyromyia lanei (6.5%), Brumptomyia nitzulescui (5.7%), Evandromyia edwardsi (5.4%), Nyssomyia intermedia (2.8%), Evandromyia cortelezzii (0.6%), Pintomyia bianchigalatiae (0.5%), Lutzomyia longipalpis (0.2%) and Sciopemyia microps (0.1%). Both Mg. migonei and Ny. intermedia may be acting as vectors of CL in this area.

The 32 kDa hydrophilic and acidic enamelin, the most stable cleavage fragment of the enamel specific glycoprotein, is believed to play vital roles in controlling crystal nucleation or growth during enamel biomineralization. Circular dichroism and Fourier transform infrared spectra demonstrate that the secondary structure of the 32 kDa enamelin has a high content of α-helix (81.5%). Quantitative analysis on the circular dichroism data revealed that the 32 kDa enamelin undergoes conformational changes with a structural preference to β-sheet as a function of calcium ions. We suggest that the increase of β-sheet conformation upon presence of Ca2+ may allow preferable interaction of the 32 kDa enamelin with apatite crystal surfaces during enamel biomineralization. The calcium association constant of the 32 kDa enamelin calculated from the fitting curve of ellipticity at 222 nm is Ka = 1.55 (±0.13) × 103 M−1, indicating a relatively low affinity. Our current biophysical studies on the 32 kDa enamelin structure provide novel insights towards understanding the enamelin-mineral interaction and subsequently the functions of enamelin during enamel formation. PMID:18508280

The 32kDa thylakoid membrane protein is an integral component of the PS II reaction centre. The protein, although stable in the dark, undergoes light dependent turnover. Light from the UV, visible and far-red spectral regions induce 32kDa protein degradation. To better understand 32kDa protein metabolism, an in vitro degradation system is being developed. It consists of isolated thylakoid membranes than contain radiolabelled protein. The 32kDa protein is actively and specifically degraded when the thylakoid preparation is exposed to UV or visible radiation. The protein is stable in the dark. The herbicides (atrazine and DCMU) inhibit degradation in the in vitro system as they do in vivo. Additionally, several methods of isolating thylakoids are being compared to optimize the 32kDa protein degradation reaction. The preparations will be evaluated based on their ability to permit light dependent degradation of the 32kDa protein without affecting the other membrane components.

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

Proteolytic enzymes hydrolyze cereal seed storage proteins into small peptides and amino acids, which are very important for seed germination and the malting process. A cysteine-class endopeptidase was purified from 4-d-germinated barley (Hordeum vulgare L. cv. Morex). Four purification steps were used, carboxymethyl cellulose cation-exchange chromatography, chromatofocusing, size-exclusion chromatography, and electroelution from a polyacrylamide gel. The endopeptidase was most active at pH 4.5. It's isoelectric point (pI) was 4.4, as determined by isoelectric focusing, and it's SDS-PAGE molecular size was 31 kDa. The enzyme specifically hydrolyzed peptide bonds when the S2 site contained relatively large hydrophobic amino acids. The N-terminal amino acid sequence residues (1-9) of the 31-kDa endopeptidase had high homology to those of the EP-A and EP-B cysteine proteinases reported previously. The 31-kDa endopeptidase had a hydrolytic specificity similar to that of the Morex green malt 30-kDa endopeptidase we characterized previously, and also reacted with the antibody raised against the purified 30-kDa proteinase, but the two had different mobilities on non-denaturing PAGE. The hydrolytic specificities of both 30- and 31-kDa endopeptidases are such that both would very quickly cleave hordein (barley storage) proteins to small glutamine- and proline-rich peptides that could be quickly degraded to amino acids by barley exopeptidases.

Leonardo da Vinci was a genius whose accomplishments and ideas come down to us today, five centuries later, with the freshness of innovation and the fascination of discovery. This brief review begins with a summary of Leonardo's life and a description of the most important works of art that he bequeathed us, and then concentrates on his last great challenge. There was a point at which Leonardo's passion for art gave way to the study of human anatomy, not only to improve his drawing but to go beyond what had been simply a representation of form to understand the underlying functioning. Among his many interests, we focus on his study of the heart and blood vessels, which he observed carefully in animals and human autopsies, and reproduced in drawings of great quality with annotations of astonishing acuteness. The experience that he had acquired from observing the flow of water in currents and around obstacles, and the conclusions that he drew concerning hydrodynamics, were central to his interpretation of the mechanisms of the heart and of blood flow, to which he devoted much of his time between 1508 and 1513. From these studies, immortalized in drawings of great clarity, come what are acknowledged to be the first hemodynamic records, in which Leonardo demonstrates the characteristics of blood flow in the aorta and great vessels and the importance of blood reflux and the formation of eddies in the sinus in aortic valve his assiduous and careful observations, and his subsequent deductions, Leonardo put forward detailed findings on hemodynamic questions that advanced technology has only recently enabled us to confirm.

The classic myelin basic protein (MBP) family of central nervous system (CNS) myelin arises from transcription start site 3 of the Golli (gene of oligodendrocyte lineage) complex and comprises splice isoforms ranging in nominal molecular mass from 14 kDa to (full-length) 21.5 kDa. We have determined here a number of distinct functional differences between the major 18.5-kDa and minor 21.5-kDa isoforms of classic MBP with respect to oligodendrocyte (OLG) proliferation. We have found that, in contrast to 18.5-kDa MBP, 21.5-kDa MBP increases proliferation of early developmental immortalized N19-OLGs by elevating the levels of phosphorylated ERK1/2 and Akt1 kinases and of ribosomal protein S6. Coculture of N2a neuronal cells with N19-OLGs transfected with the 21.5-kDa isoform (or conditioned medium from), but not the 18.5-kDa isoform, caused the N2a cells to have increased neurite outgrowth and process branching complexity. These roles were dependent on subcellular localization of 21.5-kDa MBP to the nucleus and on the exon II-encoded segment, suggesting that the nuclear localization of early minor isoforms of MBP may play a crucial role in regulating and/or initiating myelin and neuronal development in the mammalian CNS.

DA-9801, a mixture of extracts from Dioscorea japonica Thunb. and Dioscorea nipponica Makino, was reported to have neurotrophic activity. Therefore, we investigated the therapeutic potential of DA-9801, in comparison with alpha lipoic acid (ALA), for peripheral nerves preservation in experimental diabetes. Experimental animals were divided into 4 groups, and each group was designated according to the type of treatment administered as follows: normal, DM, DM+DA-9801, and DM+ALA. After 16 weeks, response thresholds to tactile and thermal stimuli were higher in DM+DA-9801 group than in nontreated DM group. This degree of increase in DM+DA-9801 group indicates more therapeutic potency of DA-9801 than ALA. Western blot analysis showed more significant increase in NGF and decrease in TNF-α and IL-6 in DM+DA-9801 group than in DM or DM+ALA groups (P < 0.05). IENF density was reduced less significantly in the DM+DA-9801 group than in other DM groups (7.61 ± 0.32, 4.2 ± 0.26, and 6.5 ± 0.30 in DM+DA-9801, DM, and DM+ALA, resp., P < 0.05). Mean myelinated axonal area in the sciatic nerves was significantly greater in DM+DA-9801 group than in other DM groups (69.2 ± 5.76, 54.0 ± 6.32, and 63.1 ± 5.41 in DM+DA-9801, DM, and DM+ALA, resp., P < 0.05). Results of this study demonstrated potential therapeutic applications of DA-9801 for the treatment of diabetic peripheral neuropathy.

The DA-T Gibbs sampler is proposed by Maris and Maris (2002) as a Bayesian estimation method for a wide variety of "Item Response Theory (IRT) models". The present paper provides an expository account of the DA-T Gibbs sampler for the 2PL model. However, the scope is not limited to the 2PL model. It is demonstrated how the DA-T Gibbs…

The M-transcript of human choline acetyltransferase (ChAT) produces an 82-kDa protein (82-kDa ChAT) that concentrates in nuclei of cholinergic neurons. We assessed the effects of acute exposure to oligomeric amyloid-β1–42 (Aβ1–42) on 82-kDa ChAT disposition in SH-SY5Y neural cells, finding that acute exposure to Aβ1–42 results in increased association of 82-kDa ChAT with chromatin and formation of 82-kDa ChAT aggregates in nuclei. When measured by chromatin immunoprecipitation with next-generation sequencing (ChIP-seq), we identified that Aβ1–42 -exposure increases 82-kDa ChAT association with gene promoters and introns. The Aβ1–42 -induced 82-kDa ChAT aggregates co-localize with special AT-rich binding protein 1 (SATB1), which anchors DNA to scaffolding/matrix attachment regions (S/MARs). SATB1 had a similar genomic association as 82-kDa ChAT, with both proteins associating with synapse and cell stress genes. After Aβ1–42 -exposure, both SATB1 and 82-kDa ChAT are enriched at the same S/MAR on the APP gene, with 82-kDa ChAT expression attenuating an increase in an isoform-specific APP mRNA transcript. Finally, 82-kDa ChAT and SATB1 have patterned genomic association at regions enriched with S/MAR binding motifs. These results demonstrate that 82-kDa ChAT and SATB1 play critical roles in the response of neural cells to acute Aβ -exposure. PMID:27052102

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry. PMID:27163287

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.

Enamel extracelluar matrix components play vital roles in controlling crystal nucleation and growth during enamel formation. We investigated the interaction between the 32 kDa enamelin fragment and amelogenin using immunochemical and biophysical methods. Immunoprecipitation studies revealed that the 32 kDa enamelin and amelogenin eluted together from a Protein A column. Dynamic light scattering results showed that the 32 kDa enamelin had a profound effect on amelogenin assembly at pH 8.0, causing partial dissociation of the nanospheres, in a dose-dependent manner. The appearance of an isodichroic point and the shifting and intensity decrease of the ellipticity minima in the circular dichroism spectra of amelogenin following the addition of the 32 kDa enamelin were indicative of conformational changes in amelogenin and of a direct interaction between the two macromolecules. Our results collectively demonstrate that the 32 kDa enamelin has a direct interaction with amelogenin in vitro. Our current studies provide novel insights into understanding possible cooperation between enamelin and amelogenin in macromolecular self-assembly and in controlling enamel mineral formation. PMID:19263522

A 36 kDa chitinase was purified by ion exchange and gel filtration chromatography from the culture supernatant of Bacillus thuringiensis HD-1. The chitinase production was independent of the presence of chitin in the growth medium and was produced even in the presence of glucose. The purified chitinase was active at acidic pH, had an optimal activity at pH 6.5, and showed maximum activity at 65 degrees C. Of the various substrates, the enzyme catalyzed the hydrolysis of the disaccharide 4-MU(GlnAc)(2) most efficiently and was therefore classified as an exochitinase. The sequence of the tryptic peptides showed extensive homology with Bacillus cereus 36 kDa exochitinase. The 1083 bp open reading frame encoding 36 kDa chitinase was amplified with primers based on the gene sequence of B. cereus 36 kDa exochitinase. The deduced amino-acid sequence showed that the protein contained an N-terminal signal peptide and consisted of a single catalytic domain. The two conserved signature sequences characteristic of family 18 chitinases were mapped at positions 105-109 and 138-145 of Chi36. The recombinant chitinase was expressed in a catalytically active form in Escherichia coli in the vector pQE-32. The expressed 36 kDa chitinase potentiated the insecticidal effect of the vegetative insecticidal protein (Vip) when used against neonate larvae of Spodoptera litura.

After a scheduled maintenance and upgrade period, the world's largest and most powerful machine - the Large Hadron Collider(LHC) - is about to enter its second run at unprecedented energies. In order to exploit the scientific potential of the machine, the experiments at the LHC face computational challenges with enormous data volumes that need to be analysed by thousand of physics users and compared to simulated data. Given diverse funding constraints, the computational resources for the LHC have been deployed in a worldwide mesh of data centres, connected to each other through Grid technologies. The PanDA (Production and Distributed Analysis) system was developed in 2005 for the ATLAS experiment on top of this heterogeneous infrastructure to seamlessly integrate the computational resources and give the users the feeling of a unique system. Since its origins, PanDA has evolved together with upcoming computing paradigms in and outside HEP, such as changes in the networking model, Cloud Computing and HPC. It is currently running steadily up to 200 thousand simultaneous cores (limited by the available resources for ATLAS), up to two million aggregated jobs per day and processes over an exabyte of data per year. The success of PanDA in ATLAS is triggering the widespread adoption and testing by other experiments. In this contribution we will give an overview of the PanDA components and focus on the new features and upcoming challenges that are relevant to the next decade of distributed computing workload management using PanDA.

Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

Trichomonas vaginalis is a flagellate protozoan parasite and commonly infected the lower genital tract in women and men. Iron is a known nutrient for growth of various pathogens, and also reported to be involved in establishment of trichomoniasis. However, the exact mechanism was not clarified. In this study, the author investigated whether the 120 kDa protein of T. vaginalis may be involved in pathogenicity of trichomonads. Antibodies against 120 kDa protein of T. vaginalis, which was identified as pyruvate:ferredoxin oxidoreductase (PFOR) by peptide analysis of MALDI-TOF-MS, were prepared in rabbits. Pretreatment of T. vaginalis with anti-120 kDa Ab decreased the proliferation and adherence to vaginal epithelial cells (MS74) of T. vaginalis. Subcutaneous tissue abscess in anti-120 kDa Ab-treated T. vaginalis-injected mice was smaller in size than that of untreated T. vaginalis-infected mice. Collectively, the 120 kDa protein expressed by iron may be involved in proliferation, adhesion to host cells, and abscess formation, thereby may influence on the pathogenicity of T. vaginalis.

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

The PanDA (Production and Distributed Analysis) system has been developed to meet ATLAS production and analysis requirements for a data-driven workload management system capable of operating at LHC data processing scale. PanDA has performed well with high reliability and robustness during the two years of LHC data-taking, while being actively evolved to meet the rapidly changing requirements for analysis use cases. We will present an overview of system evolution including automatic rebrokerage and reattempt for analysis jobs, adaptation for the CernVM File System, support for the multi-cloud model through which Tier-2 sites act as members of multiple clouds, pledged resource management and preferential brokerage, and monitoring improvements. We will also describe results from the analysis of two years of PanDA usage statistics, current issues, and plans for the future.

New soft X-ray/EUV photometric observations of the DA white dwarfs KPD 0631 + 1043 = WD 0631 + 107 and PG 1113 + 413 = WD 1113 + 413 are analyzed. Previously reported soft X-ray detections of three other DAs and the failure to detect a fourth DA in deep Exosat observations are investigated. New ground-based spectra are presented for all of the objects, with IUE Ly-alpha spectra for some. These data are used to constrain the effective temperatures and surface gravities. The improved estimates of these parameters are employed to refer a photospheric He abundance for the hotter objects and to elucidate an effective observational low-temperature threshold for the detection of pure hydrogen DA white dwarfs at soft X-ray wavelengths.

We present here the organization of the recently-constituted da Vinci European BioBank (daVEB, https://www.davincieuropeanbiobank.org/it). The biobank was created as an infrastructure to support the activities of the Fiorgen Foundation (http://www.fiorgen.net/), a nonprofit organization that promotes research in the field of pharmacogenomics and personalized medicine. The way operating procedures concerning samples and data have been developed at daVEB largely stems from the strong metabolomics connotation of Fiorgen and from the involvement of the scientific collaborators of the foundation in international/European projects aimed to tackle the standardization of pre-analytical procedures and the promotion of data standards in metabolomics. PMID:25913579

ATLAS user jobs are executed on Worker Nodes (WNs) by pilots sent to sites by pilot factories. This paradigm serves to allow a high job reliability and although it has clear advantages, such as making the working environment homogeneous, the approach presents security and traceability challenges. To address these challenges, gLExec can be used to let the payloads for each user be executed under a different UNIX user id that uniquely identifies the ATLAS user. This paper describes the recent improvements and evolution of the security model within the ATLAS PanDA system, including improvements in the PanDA pilot, in the PanDA server and their integration with MyProxy, a credential caching system that entitles a person or a service to act in the name of the issuer of the credential. Finally, it presents results from ATLAS user jobs running with gLExec and describes the deployment campaign within ATLAS.

Fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC) and Partial least squares Discriminant Analysis (PLS DA) were used for characterization and classification of honey. Excitation emission spectra were obtained for 95 honey samples of different botanical origin (acacia, sunflower, linden, meadow, and fake honey) by recording emission from 270 to 640 nm with excitation in the range of 240-500 nm. The number of fluorophores present in honey, excitation and emission spectra of each fluorophore, and their relative concentration are determined using a six-component PARAFAC model. Emissions from phenolic compounds and Maillard reaction products exhibited the largest difference among classes of honey of different botanical origin. The PLS DA classification model, constructed from PARAFAC model scores, detected fake honey samples with 100% sensitivity and specificity. Honey samples were also classified using PLS DA with errors of 0.5% for linden, 10% for acacia, and about 20% for both sunflower and meadow mix.

1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2. Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3. CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

Follow-up spectroscopy of several hundred hot stars detected by the Hamburg Quasar Survey (HQS) has been carried out between 1989 and 1996. We present the analysis of 80 DA white dwarfs using model atmospheres and theoretical cooling tracks to derive the atmospheric parameters T_eff and log g, masses and absolute magnitudes. The HQS turned out to be sensitive to the detection of hydrogen-rich white dwarfs in a wide temperature range, from 10 000 K upwards. Star counts within four HQS fields for magnitudes B<= 16fm 4 exceed those from the Palomar Green survey by about 50%. The more recent observation campaigns emphasized the detection of very hot degenerates, yielding a large fraction of DA stars with T_eff > 50 000 K compared to other surveys. The mean mass of our DA sample is M=0.61{M}_{\\odot}, with three massive DA stars exceeding 1{M}_{\\odot} and three DA stars with masses significantly below the assummed lower mass limit for single white dwarf evolution of 0.45{M}_{\\odot}. Among the cool DA stars, thirteen are potential ZZ Ceti candidates because their effective temperatures lie close to the instability strip. Based on observations collected at the German-Spanish Astronomical Center (DSAZ), Calar Alto, operated by the Max-Plank-Institut für Astronomie Heidelberg jointly with the Spanish National Commission for Astronomy; with the International Ultraviolet Explorer satellite (IUE) collected at Villafranca, Spain, and with the ROSAT X-ray telescope.

The PanDA (Production and Distributed Analysis) workload management system (WMS) was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. While PanDA currently distributes jobs to more than 100,000 cores at well over 100 Grid sites, the future LHC data taking runs will require more resources than Grid computing can possibly provide. To alleviate these challenges, ATLAS is engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF). The current approach utilizes a modified PanDA pilot framework for job submission to Titan's batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on Titan's multicore worker nodes. It also gives PanDA new capability to collect, in real time, information about unused worker nodes on Titan, which allows precise definition of the size and duration of jobs submitted to Titan according to available free resources. This capability significantly reduces PanDA job wait time while improving Titan's utilization efficiency. This implementation was tested with a variety of Monte-Carlo workloads on Titan and is being tested on several other supercomputing platforms. Notice: This manuscript has been authored, by employees of Brookhaven Science Associates, LLC under Contract No. DE-AC02-98CH10886 with the U.S. Department of Energy. The publisher by accepting the manuscript for publication acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

We present new observations of the `supernova impostor' SN 2010da using the Chandra X-ray Observatory and the Hubble Space Telescope. During the initial 2010 outburst, the 0.3-10 keV luminosity was observed by Swift to be ˜5 × 1038 erg s-1 and faded by a factor of ˜25 in a four month period. Our two new Chandra observations show a factor of ˜10 increase in the 0.35-8 keV X-ray luminosity, from ˜4 × 1036 to 4 × 1037 erg s-1 in ˜6 months, and the X-ray spectrum is consistent in both observations with a power-law with a photon index of Γ ˜ 0. We find evidence of X-ray spectral state changes: when SN 2010da is in a high-luminosity state, the X-ray spectrum is harder (Γ ˜0) compared to the low-luminosity state (Γ ˜ 1.2 ± 0.8). Using our Hubble observations, we fit the colour-magnitude diagram of the coeval stellar population to estimate a time since formation of the SN 2010da progenitor system of ≲5 Myr. Our observations are consistent with SN 2010da being a high-mass X-ray binary (HMXB) composed of a neutron star and a luminous blue variable-like companion, although we cannot rule out the possibility that SN 2010da is an unusually X-ray bright massive star. The ≲5 Myr age is consistent with the theoretically predicted delay time between the formation of a massive binary and the onset of the HMXB phase. It is possible that the initial 2010 outburst marked the beginning of X-ray production in the system, making SN 2010da possibly the first massive progenitor binary ever observed to evolve into an HMXB.

A mineral phosphate solubilizing bacterium, Burkholderia cepacia DA23 has been isolated from cultivated soils. Phosphate-solubilizing activities of the strain against three types of insoluble phosphate were quantitatively determined. When 3% of glucose concentration was used for carbon source, the strain had a marked mineral phosphate-solubilizing activity. Mineral phosphate solubilization was directly related to the pH drop by the strain. Analysis of the culture medium by high pressure liquid chromatography identified gluconic acid as the main organic acid released by Burkholderia cepacia DA23. Gluconic acid production was apparently the result of the glucose dehydrogenase activity and glucose dehydrogenase was affected by phosphate regulation. PMID:24031195

A method for the automatic calculation of the atmospheric parameters (Teff and log g) of hydrogen-rich degenerate stars from low-resolution spectra is described, and then applied to the spectra of 53 DA white dwarfs. A value for the width of the DA mass distribution of sigma M/solar-M not greater than +0.10 is obtained using the proposed approach. The data indicate that the distribution is asymmetrically skewed to low masses; however, there is also evidence of a high-mass non-Gaussian tail.

Da Vinci robot is increasingly used for operations adding the advantages of robots to the favor of medicine. This is a historical article with the aim to present the evolution of robots in the medical area from the time of ancient myths to Renaissance and finally to the current revolutionary applications. We endeavored to collect several elegant narratives on the topic. The use of imagination could help the reader to find similarities. A trip from the Greek myths of Hephaestus through Aristotle and Leonardo Da Vinci to the robots of Karel Capek and Isaac Asimov and finally the invention of the medical robots is presented.

An 80-year-old man with Parkinson disease underwent DaTscan imaging, which showed no detectable uptake in the basal ganglia but normal background uptake in other parts of the brain and in the chest and abdomen. It was later found that the patient was taking methylphenidate. The second study performed 3 weeks later after discontinuing methylphenidate for 48 hours showed good uptake in the striatum. Our results indicate that methylphenidate may completely block physiologic uptake of DaTscan in the striatum and that this effect can be effectively reversed after discontinuing the medication for a short period.

The da Vinci system (da Vinci Surgical System; Intuitive Surgical Inc.) has rapidly developed in several years from the S system to the Si system and now the Xi System. To investigate the surgical feasibility and to provide workflow guidance for the newly released system, we used the new da Vinci Xi system for transoral robotic surgery (TORS) on a cadaveric specimen. Bilateral supraglottic partial laryngectomy, hypopharyngectomy, lateral oropharyngectomy, and base of the tongue resection were serially performed in search of the optimal procedures with the new system. The new surgical robotic system has been upgraded in all respects. The telescope and camera were incorporated into one system, with a digital end-mounted camera. Overhead boom rotation allows multiquadrant access without axis limitation, the arms are now thinner and longer with grabbing movements for easy adjustments. The patient clearance button dramatically reduces external collisions. The new surgical robotic system has been optimized for improved anatomic access, with better-equipped appurtenances. This cadaveric study of TORS offers guidance on the best protocol for surgical workflow with the new Xi system leading to improvements in the functional results of TORS.

The impairment of protein degradation via the ubiquitin-proteasome system (UPS) is present in sporadic Parkinson's disease (PD), and might play a key role in selective degeneration of vulnerable dopamine (DA) neurons in the substantia nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS in familial PD comes from mutations in parkin, which results in a loss of function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an essential component of the 26S proteasome lead to widespread neuronal degeneration including DA midbrain neurons and the formation of alpha-synuclein-positive inclusion bodies, another hallmark of PD. Studies using pharmacological UPS inhibition in vivo had more mixed results, varying from extensive degeneration to no loss of DA SN neurons. However, it is currently unknown whether UPS impairment will affect the neurophysiological functions of DA midbrain neurons. To answer this question, we infused a selective proteasome inhibitor into the ventral midbrain in vivo and recorded single DA midbrain neurons 2 weeks after the proteasome challenge. We found a selective increase in the mean in vivo firing frequencies of identified DA SN neurons in anesthetized mice, while those in the ventral tegmental area (VTA) were unaffected. Our results demonstrate that a single-hit UPS inhibition is sufficient to induce a stable and selective hyperexcitability phenotype in surviving DA SN neurons in vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing 'stressful pacemaking'.

Rhubarb (official Da-huang) is an important medicinal herb in Asia. Many adulterants of official Da-huang have been discovered in Chinese markets in recent years, which has resulted in adverse effects in medicinal treatment. Here, novel molecular markers based on a short maturase K (matK) gene were developed for authenticating official Da-huang. This study showed that all the species from official Da-huang were clustered together in one clade in the polygenetic trees based on short matK. Two highly conserved single nucleotide polymorphisms of short matK were mined in the species from official Da-huang. Based on these polymophisms, four improved specific primers of official Da-huang were successfully developed that generated reproducible specific bands. These results suggest that the short matK sequence can be considered as a favorable candidate for distinguishing official Da-huang from its adulterants. The established multiplex allele-specific PCR was determined to be simple and accurate and may serve as a preferable tool for authentication of official Da-huang. In addition, we suggest that short-sized specific bands be developed to authenticate materials used in traditional Chinese medicine.

AIM: To determine the efficacy and safety of DA-9601 on erosive gastritis versus cetraxate as a standard drug by gastrointestinal endoscopy. METHODS: Five hundred and twelve patients with erosive gastritis were divided into three groups. The groups received 180 mg or 360 mg of DA-9601, or 600 mg of cetraxate (NeuerTM) t.i.d. for 2 wk, respectively. Endoscopic observations were performed before and 2 wk after the treatment, and the cure and improvement rates were investigated. RESULTS: Of the 512 intention-to-treat (ITT) population, 457 patients comprised the per protocol (PP) analysis. Endoscopic cure rate was significantly higher in the DA-9601 group than in the cetraxate group in both the PP (56%, 58% vs 36%; DA-9601 180 mg, 360 mg and cetraxate, respectively) and ITT (52%, 51% vs 35%) populations. Two DA-9601 groups (180 and 360 mg) had significantly higher endoscopic improvement rates than the cetraxate group in both the PP (67%, 65% vs 46%) and ITT (63%, 58% vs 45%) populations. The percentage of symptom relief over the 2 wk was found not significantly different between groups. During the study, both DA-9601 and cetraxate produced no treatment-associated adverse events. CONCLUSION: From these results, it appears that DA-9601 has excellent efficacy on erosive gastritis. This study also confirms the safety profile of DA-9601. PMID:15285023

The 37/67 kDa laminin receptor (LR) is a non-integrin protein, which binds both laminin-1 of the extracellular matrix and prion proteins, that hold a central role in prion diseases. The 37/67 kDa LR has been identified as interactor for the prion protein (PrPC) and to be required for pathological PrP (PrPSc) propagation in scrapie-infected neuronal cells, leading to the possibility that 37/67 kDa LR-PrPC interaction is related to the pathogenesis of prion diseases. A relationship between 37/67 kDa LR and PrPC in the presence of specific LR inhibitor compounds has not been investigated yet. We have characterized the trafficking of 37/67 kDa LR in both neuronal and non-neuronal cells, finding the receptor on the cell surface and nuclei, and identified the 67 kDa LR as the almost exclusive isoform interacting with PrPC. Here, we show that the treatment with the 37/67 kDa LR inhibitor, NSC47924, affects both the direct 37/67 kDa LR-PrPC interaction in vitro and the formation of the immunocomplex in live cells, inducing a progressive internalization of 37/67 kDa LR and stabilization of PrPC on the cell surface. These data reveal NSC47924 as a useful tool to regulate PrPC and 37/67 kDa LR trafficking and degradation, representing a novel small molecule to be tested against prion diseases. PMID:27071549

The issues of how to avoid future surprise growth in Mission Operations and Data Analysis (MO&DA) costs and how to minimize total MO&DA costs for planetary missions are discussed within the context of JPL mission operations support. It is argued that there is no simple, single solution: the entire Project life-cycle must be addressed. It is concluded that cost models that can predict both MO&DA cost as well as Ground System development costs are needed. The first year MO&DA budget plotted against the total of ground and flight systems developments is shown. In order to better recognize changes and control costs in general, a modified funding line item breakdown is recommended to distinguish between development costs (prelaunch and postlaunch) and MO&DA costs.

Background/Aims DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. Methods A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Results Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. Conclusions DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition. PMID:26755679

In {sup 32}P{sub i}-loaded bovine neutrophils stimulated with phorbol myristate acetate (PMA), radioactivity was preferentially incorporated into a protein of low molecular mass, suggesting a PKC-dependent phosphorylation. This protein, termed 23-kDa protein, was predominantly localized in the cytosol. The apparent molecular mass of the purified protein range between 20 and 23 kDa. In the absence of mercaptoethanol, a dimer accumulated. Homogeneity of the 23-kDa protein was verified by 2D-PAGE analysis. Gel isoelectric focusing (IEF) of the purified 23-kDa protein followed by Coomassie blue staining allowed the visualization of our discrete protein bands with isoelectric points ranging between pH 6.3 and 6.7. Phosphorylation of the 23-kDa protein by ({gamma}-{sup 32}P)ATP in the presence of bovine neutrophil PKC supplemented with Ca{sup 2+}, phosphatidylserine, and diacylglycerol or with PMA occurred on serine and required the presence of mercaptoethanol. IEF of the {sup 32}P-labeled 23-kDa protein followed by autoradiography revealed for discrete bands with distinct isoelectric points similar to those of the bands stained by Coomassie blue after IEF on nonlabeled 23-kDa protein. The bands of the 23-kDa protein resolved by IEF and transfered to nitrocellulose showed ability to bind ({sup 35}S)GTP-{gamma}-S. The immunoreactivity of antibodies raised in rabbits against the bovine neutrophil 23-kDa protein was demonstrated on immunoblots after SDS-PAGE. The 23-kDa protein differed also from several other proteins of similar molecular mass that have been identified in neutrophils, namely, calmodulin, the small subunit of the low-potential cytochrome b, and a low molecular weight protein which is ADP-ribosylated by the botulinum toxin.

Objective DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. Methods A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. Results After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2–3 h and was eliminated with terminal elimination half-life of 17.9–28.7 h. The mean renal clearance was 3.7–5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20–80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0–t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. Conclusion In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20–80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less. PMID:28331291

At the Sixth Annual Reunion of the Brazilian Association of Medical Schools (VI Reuniao Anual da Associacao Brasileira de Escolas Medicas) leaders in the Brazilian medical profession proposed an integrated educational program for training students in the fields of medicine and public health. Under Brazil's present system of education, all…

Dynamic assessment (DA) derives from the sociocultural theory of mind as elaborated by Russian psychologist L. S. Vygotsky. By offering mediation when individuals experience difficulties and carefully tracing their responsiveness, Vygotsky (1998) proposed that diagnoses may uncover abilities that have fully formed as well as those still in the…

This dissertation investigates the contextual factors that affect the understanding and interpretation of one Japanese topicalized construction, NP[subscript 1] wa NP[subscript 2] da sentences, by native speakers of Japanese. The construction allows two possibilities in the relation between the NP[subscript 1] and the NP[subscript 2]. When the two…

Evolution of the ATLAS PanDA Production and Distributed Analysis System T Maeno1,5, K De2, T Wenaus1, P Nilsson2, R Walker3, A Stradling2, V Fine1, M Potekhin1, S Panitkin1 and G Compostella4 Published under licence by IOP Publishing Ltd Journal of Physics: Conference Series, Volume 396, Part 3 Article PDF References Citations Metrics 101 Total downloads Cited by 8 articles Turn on MathJax Share this article Article information Abstract The PanDA (Production and Distributed Analysis) system has been developed to meet ATLAS production and analysis requirements for a data-driven workload management system capable of operating at LHC data processing scale. PanDA has performed well with high reliability and robustness during the two years of LHC data-taking, while being actively evolved to meet the rapidly changing requirements for analysis use cases. We will present an overview of system evolution including automatic rebrokerage and reattempt for analysis jobs, adaptation for the CernVM File System, support for the multi-cloud model through which Tier-2 sites act as members of multiple clouds, pledged resource management and preferential brokerage, and monitoring improvements. We will also describe results from the analysis of two years of PanDA usage statistics, current issues, and plans for the future.

In 2005, Spanish television audiences saw the debut of the nation's first spinoff, the sitcom "Aída." The show featured the tribulations of its title character and her working-class family in their struggle to "llegar a fin de mes." It seemed to promise a sensibility enacted in the US series "Roseanne," where another…

The aims of the study were to differentiate Pueraria lobata from its related species Pueraria thomsonii and to examine the raw herbal material used in manufacturing kudzu root granules using partial least square discriminant analysis (PLS-DA). Sixty-four raw materials of P. lobata and P. thomsonii and kudzu root-labelled granules were analysed by ultra performance liquid chromatography. To differentiate P. lobata from P. thomsonii, PLS-DA models using the variables selected from the entire chromatograms, genetic algorithm (GA), successive projection algorithm (SPA), puerarin alone and six selected peaks were employed. The models constructed by GA and SPA demonstrated superior classification ability and lower model's complexity as compared to the model based on the entire chromatographic matrix, whilst the model constructed by the six selected peaks was comparable to the entire chromatographic model. The model established by puerarin alone showed inferior classification ability. In addition, the PLS-DA models constructed by the entire chromatographic matrix, GA, SPA and the six selected peaks showed that four brands out of seventeen granules were mislabelled as P. lobata. In conclusion, PLS-DA is a promising procedure for differentiating Pueraria species and determining raw material used in commercial products.

MP (Ritalin) is a psychomotor stimulant used in the treatment of attention-deficit hyperactivity disorder. The therapeutic properties of MP are thought to be mediated by its binding to a site on the DA transporter, resulting in inhibition of DA reuptake and enhanced levels of synaptic dopamine. MP also inhibits reuptake of norepinephrine (NE) in vitro. MP has two chiral centers, but its pharmacological activity is believed due solely to the d-threo isomer. We have found that d,l-threo-C-11 MP has favorable properties for PET studies, and therefore examined the effects of incorporating halogen atoms into the phenyl ring of MP, with a view to preparing C-11 and I-123 MP analogs as potential PET/SPECT tracers. We synthesized the 2-, 3- and 4-bromo MP analogs from the corresponding bromophenylacetonitriles by modification of the original synthesis of MP. In in vitro binding assays all three d,l-threo bromo compounds had higher affinities than MP for DA transporter sites labeled with tritiated WIN 35,428 (3->4-, 2->MP). They also showed high activity with NE reuptake sites labeled with tritiated nisoxetine. They were active in vivo as demonstrated by inhibition of heart uptake of tritiated NE in the mouse, and elevation of striatal extracellular DA (microdialysis) and stimulation of locomotor activity in the rat.

Susceptibility of oats to victoria blight, caused by the fungus Cochliobolus victoriae, and sensitivity to the host-specific toxin victorin, produced by the fungus, are controlled by the dominant allele at the Vb locus. It has been postulated that the Vb locus encodes a toxin receptor, although direct evidence for such a receptor is not available. Recent studies on structure-activity relationships of the toxin established a methodology for producing {sup 125}I-labeled victorin. Electrophoretic analysis of proteins from isogenic susceptible and resistant oat genotypes following treatment of leaves with radiolabeled victorin showed that victorin binds in a covalent and a genotype-specific manner to a 100-kDa protein only in susceptible oat leaf slices. This in vivo binding was competitively displaced by reduced victorin, a nontoxic protective compound, and appeared to be correlated with biological activity. In vitro binding to the 100-kDa protein in leaf extracts showed several differences from in vivo binding. Binding was not genotype specific and required a reducing agent that was not required for in vivo binding. Differential centrifugation showed that the 100-kDa victorin binding protein was not a cytosolic protein but was enriched in a high-speed particulate fraction. The data support the hypothesis that the 100-kDa protein is the victorin receptor.

We agree with Dr. da Silva, and wish to clarify three issues raised by the recent IOM report concerning our 2009 meta-analysis on vitamin D and fall prevention. 1. The IOM questioned the inclusion of Broe et al., which did not pre-specify falls as a primary or secondary outcome. While this did viol...

This report gives an overview of the situation of transparency of vocational qualifications by presenting measures introduced at the European Community level and by drawing attention to projects within the Leonardo da Vinci Program dealing with the issue. A 16-page executive summary appears first. Chapter 1 provides general background and aims.…

Discusses the success of the Leonardo da Vinci program, a European laboratory of innovation in vocational training, a priority focus of investment in human resources and intelligence, and a way to mobilize innovative forces beyond national boundaries. Trends identified by the program focus on new information and communication technologies. (JOW)

The symbiotic bacterium Holospora obtusa infects the macronucleus of the ciliate Paramecium caudatum. After ingestion by its host, an infectious form of Holospora with an electron-translucent tip passes through the host digestive vacuole and penetrates the macronuclear envelope with this tip. To investigate the underlying molecular mechanism of this process, we raised a monoclonal antibody against the tip-specific 89-kDa protein, sequenced this partially, and identified the corresponding complete gene. The deduced protein sequence carries two actin-binding motifs. Indirect immunofluorescence microscopy shows that during escape from the host digestive vacuole, the 89-kDa proteins translocates from the inside to the outside of the tip. When the bacterium invades the macronucleus, the 89-kDa protein is left behind at the entry point of the nuclear envelope. Transmission electron microscopy shows the formation of fine fibrous structures that co-localize with the antibody-labeled regions of the bacterium. Our findings suggest that the 89-kDa protein plays a role in Holospora's escape from the host digestive vacuole, the migration through the host cytoplasm, and the invasion into the macronucleus.

We propose a new model for da Vinci stereopsis based on a coarse-to-fine disparity-energy computation in V1 and disparity-boundary-selective units in V2. Unlike previous work, our model contains only binocular cells, relies on distributed representations of disparity, and has a simple V1-to-V2 feedforward structure. We demonstrate with random dot stereograms that the V2 stage of our model is able to determine the location and the eye-of-origin of monocularly occluded regions and improve disparity map computation. We also examine a few related issues. First, we argue that since monocular regions are binocularly defined, they cannot generally be detected by monocular cells. Second, we show that our coarse-to-fine V1 model for conventional stereopsis explains double matching in Panum’s limiting case. This provides computational support to the notion that the perceived depth of a monocular bar next to a binocular rectangle may not be da Vinci stereopsis per se (Gillam et al., 2003). Third, we demonstrate that some stimuli previously deemed invalid have simple, valid geometric interpretations. Our work suggests that studies of da Vinci stereopsis should focus on stimuli more general than the bar-and-rectangle type and that disparity-boundary-selective V2 cells may provide a simple physiological mechanism for da Vinci stereopsis. PMID:17698163

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The drug release characteristics ofDa Chuanxiong Fang multiunit drug delivery system (DCXFMDDS) in vivo and in vitro were evaluated. Ferulic acid (FA) and senkyunolide I (SI) were used as marker components, which were two of the effective components of Da Chuanxiong Fang. And their contents were determined by HPLC. Drug release characteristics in vitro of DCXFMDDS and Da Chuanxiong pills and pharmacokinetics characteristics of DCXFMDDS and Da Chuanxiong Fang active fraction (DCXFAF) in rats were compared. It was obvious that FA released from the DCXFMDDS in a sustained fashion but SI in a fast fashion both in vitro and in vivo. The releasing process and the releasing mechanism of FA and SI from DCXFMDDS were different, but the AUC value indicated that compared with DCXFAF the extent of absorption of FA and SI from DCXFMDDS was increased. Though from the same multiunit drug delivery system, FA an SI had different drug release characteristics both in vitro and in vivo, and that may be one of the reason why DCXFMDDS has the good properties such as rapid and long-lasting effect and high efficiency.

The long-term dynamical evolution of 21 variational orbits for the intermediate-period asteroid 1991 DA was followed for up to +/-10(exp 5) years from the present. 1991 DA is close to the 2:7 resonance with Jupiter; it has avoided close encounters, within 1 AU, with this planet for at least the past 30,000 years, even at the node crossing. The future evolution typically shows no close encounters with Jupiter within at least 50,000 years. This corresponds to the mean time between node crossings with either Jupiter or Saturn. Close encounters with Saturn and Jupiter lead to a chaotic evolution for the whole ensemble, while secular perturbations cause large-amplitude swings in eccentricity and inclination (the latter covering the range 15 deg approximately less than i approximately less than 85 deg) which correlate with deep excursions of the perihelion distance to values much less than 1 AU. These variations are similar to those found in P/Machholz and a variety of other high-inclination orbits, e.g., P/Hartley-IRAS. We emphasize the connection between the orbital evolution of 1991 DA and that of Halley-type comets. If 1991 DA was once a comet, it is not surprising that it is now extinct.

Endoscopic surgery for treatment of thyroid and parathyroid pathologies is increasingly gaining attention. The da Vinci system has already been widely used in different fields of medicine and quite recently in thyroid and parathyroid surgery. Herein, we report about modifications of the transaxillary approach in endoscopic surgery of thyroid and parathyroid gland pathologies using the da Vinci system. 16 patients suffering from struma nodosa in 14 cases and parathyroid adenomas in two cases were treated using the da Vinci system at the ENT Department of Homburg/Saar University and in cooperation with the Department of General Surgery in New Sant'Agostino Hospital, Modena/Italy. Two different retractors, endoscopic preparation of the access and three different incision modalities were used. The endoscopic preparation of the access allowed us to have a better view during preparation and reduced surgical time compared to the use of a headlamp. To introduce the da Vinci instruments at the end of the access preparation, the skin incisions were over the axilla with one incision in eight patients, two incisions in four patients and three incisions in a further four patients. The two and three skin incisions modality allowed introduction of the da Vinci instruments without arm conflicts. The use of a new retractor (Modena retractor) compared to a self-developed retractor made it easier during the endoscopic preparation of the access and the reposition of the retractor. The scar was hidden in the axilla and independent of the incisions selected, the cosmetic findings were judged by the patients to be excellent. The neurovascular structures such as inferior laryngeal nerve, superior laryngeal nerve and vessels, as well as the different pathologies, were clearly 3D visualized in all 16 cases. No paralysis of the vocal cord was observed. All patients had a benign pathology in their histological examination. The endoscopic surgery of the thyroid and parathyroid gland can be

The.LHC, operating at CERN, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System for managing the workflow for all data processing on over 150 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250,000 cores with a peak performance of 0.3 petaFLOPS, LHC data taking runs require more resources than grid can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility. Current approach utilizes modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on LCFs multi-core worker nodes. This implementation was tested with a variety of Monte-Carlo workloads on several supercomputing platforms for ALICE and ATLAS experiments and it is in full pro duction for the ATLAS since September 2015. We will present our current accomplishments with running PanDA at supercomputers and demonstrate our ability to use PanDA as a portal independent of the

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System for managing the workflow for all data processing on over 150 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250,000 cores with a peak performance of 0.3 petaFLOPS, LHC data taking runs require more resources than Grid computing can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, Europe and Russia (in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF), MIRA supercomputer at Argonne Leadership Computing Facilities (ALCF), Supercomputer at the National Research Center Kurchatov Institute , IT4 in Ostrava and others). Current approach utilizes modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on LCFs multi-core worker nodes. This implementation

In the current study, cross-reaction between two important zoonotic parasites; extracellular helminthes Fasciola gigantica and intracellular protozoa Toxoplasma gondii was proved by enzyme linked immunosorbent assay. Five antigens were used to identify and compare the cross-binding activities in the prepared antisera. Two F. gigantica antigens; adult flukes (FgA) and eggs (FgEA) were used to detect IgG in T. gondii naturally infected human sera (TgIHS) and experimentally infected sera of sheep (TgISS), mice (TgIMS) and rats (TgIRS). Three types of T. gondii antigens; RH (TgRHA), local sheep isolate (TgLA) and ME49 isolate (TgMEA) were used to detect cross binding activities in F. gigantica experimental infected rabbit sera (FgIRS) and F. gigantica naturally infected bovine sera (FgIBS). The cross-binding activities in the prepared antisera were strongly directed towards FgA and TgLA rather than the other antigens. The characterization of the five antigens using SDS-PAGE showed 4 common bands of FgA and TgLA; 165, 97, 76, and 65 kDa. While two common bands were observed between TgRHA, TgMEA and FgA; 165, and 65 kDa. Whereas, two common bands found between three types of T. gondii antigens and FgEA were identified; 165 and 65 kDa. The immunogenic cross-reactive bands between FgA and TgLA with F. gigantica infected bovine sera were identified by immunoblot. In FgA, the common immunogenic bands were 165, 65 and 14 kDa. While in TgLA, common immunogenic bands were 165 and 65 kDa. Whereas, the common immunogenic band between FgA and TgLA identified with T. gondii experimentally infected sheep sera was 65 kDa. The current research proves cross reaction between F. gigantica and T. gondii. One common band of 65 kDa showed broad immunogenic cross-reactivity with the developed antisera raising the prospect of being putative common immunodiagnostic candidate of both infections.

We present the observation campaign for the near-Earth object 2012 DA_{14} (hereafter, DA_{14}). The asteroid DA_{14} came close to the Earth's surface on 2013 February 15, 19:33 UT, at a distance of 27,700 km. DA_{14}'s altitude from the horizon in Japan was ˜ 30° at the closest approach time. The estimated diameter of DA_{14} is ˜50 m. The close encounter and the horizontal altitude made it possible to conduct a variety of observations for this tiny asteroid using small- and medium-sized telescopes. There have been few detailed observations, including spectroscopy, of asteroids smaller than 100 m in diameter. Moreover, the close encounter might results in a change for the rotational period and the surface spectrum due to the tidal forces. The observations around the closest approach are useful to investigate such physical changes. We performed visible spectroscopy, near-infrared photometry, and time-series photometry in the visible wavelength region. The visible spectroscopy was conducted using the 0.4-m F/10 telescope at the Fujii Kurosaki Observatory. The observations aimed to deduce the taxonomy of DA_{14}. The near-infrared photometry was made by Nishiharima Infrared Camera (NIC) attached to the 2.0-m Nayuta telescope at the Nishi-Harima Astronomical Observatory. The NIC achieves three-band (i.e., J, H, and K_{s}) simultaneous observations, which allowed us to reliably deduce the colors of this fast-moving object. The time-series photometry was carried out using the 0.55-m telescope at Saitama University. The solar phase angle of DA_{14} had varied widely around its closest approach but was almost constant during the following night. The R-band images were obtained continuously over 2 h at the closest approach and for about 5 h on the subsequent night. Those two nights of observations allow us to determine the rotational properties and the phase effect. We found, from the visible spectroscopy [1], that DA_{14} is an L-type asteroid. The flatness of the

PanDA (Production and Distributed Analysis) is the workload management system of the ATLAS experiment, used to run managed production and user analysis jobs on the grid. As a late-binding, pilot-based system, the maintenance of a smooth and steady stream of pilot jobs to all grid sites is critical for PanDA operation. The ATLAS Computing Facility (ACF) at BNL, as the ATLAS Tier1 center in the US, operates the pilot submission systems for the US. This is done using the PanDA "AutoPilot" scheduler component which submits pilot jobs via Condor-G, a grid job scheduling system developed at the University of Wisconsin-Madison. In this paper, we discuss the operation and performance of the Condor-G pilot submission at BNL, with emphasis on the challenges and issues encountered in the real grid production environment. With the close collaboration of Condor and PanDA teams, the scalability and stability of the overall system has been greatly improved over the last year. We review improvements made to Condor-G resulting from this collaboration, including isolation of site-based issues by running a separate Gridmanager for each remote site, introduction of the 'Nonessential' job attribute to allow Condor to optimize its behavior for the specific character of pilot jobs, better understanding and handling of the Gridmonitor process, as well as better scheduling in the PanDA pilot scheduler component. We will also cover the monitoring of the health of the system.

PanDA (Production and Distributed Analysis) is the workload management system of the ATLAS experiment, used to run managed production and user analysis jobs on the grid. As a late-binding, pilot-based system, the maintenance of a smooth and steady stream of pilot jobs to all grid sites is critical for PanDA operation. The ATLAS Computing Facility (ACF) at BNL, as the ATLAS Tier1 center in the US, operates the pilot submission systems for the US. This is done using the PanDA 'AutoPilot' scheduler component which submits pilot jobs via Condor-G, a grid job scheduling system developed at the University of Wisconsin-Madison. In this paper, we discuss the operation and performance of the Condor-G pilot submission at BNL, with emphasis on the challenges and issues encountered in the real grid production environment. With the close collaboration of Condor and PanDA teams, the scalability and stability of the overall system has been greatly improved over the last year. We review improvements made to Condor-G resulting from this collaboration, including isolation of site-based issues by running a separate Gridmanager for each remote site, introduction of the 'Nonessential' job attribute to allow Condor to optimize its behavior for the specific character of pilot jobs, better understanding and handling of the Gridmonitor process, as well as better scheduling in the PanDA pilot scheduler component. We will also cover the monitoring of the health of the system.

Terceira island (Azores) have experienced several strong earthquakes, especially on the eastern and south-eastern part of the island with maximum MM intensity of VIII in 1800, 1801 and 1912 and IX in 1614 and 1841. Seismicity of the eastern part of the island is largely dominated by the tectonic of the NW-SE Lajes graben where are located Praia da Vitória and other setlements. Praia da Vitória is settled partially over pyroclastic material(pumice and ignimbrite) deposited around 20'000 years ago and forming part of the UpperTerceira Group. Its thickness is 15m on the north but in Praia da Vitoria has less than one meter.. It is sited on by basaltic flow of the upper Basaltic Terceira Group (2,000y BP) and a thick andesitic lava flow. A narrow band with sand dunes and beach crossed this deposits along Praia da Vitória and behind it appear a flat area with 7-10m of round cobbles that is interpreted as an old boulders'beach. Thickness of these different deposits are tricky to estimate in urban areas since very few outcrops are present. In order to assess site amplification of seismic waves due to the soil conditions, we perform horizontal-to-vertical spectral ratio (HVSR) method from broad band ambient noise measurements in 51 different sites within Praia da Vitoria. The first results show that the frequencies of the study area are variable, lying between 0.6-12 Hz. ACKNOWLEDGMENTS: João Fontiela is supported by grant M3.1.2/F/060/2011 provided by the Regional Science Fund of the Azores Regional Government. This study was partially funded by the Institute of Earth Sciences, Portugal, under the contract with the FCT, ICT-UID/GEO/04683/2013 (Portugal).

The possibility of devising a simple, flexible and accurate non-linear classification method, by extending the locally weighted partial least squares (LW-PLS) approach to the cases where the algorithm is used in a discriminant way (partial least squares discriminant analysis, PLS-DA), is presented. In particular, to assess which category an unknown sample belongs to, the proposed algorithm operates by identifying which training objects are most similar to the one to be predicted and building a PLS-DA model using these calibration samples only. Moreover, the influence of the selected training samples on the local model can be further modulated by adopting a not uniform distance-based weighting scheme which allows the farthest calibration objects to have less impact than the closest ones. The performances of the proposed locally weighted-partial least squares-discriminant analysis (LW-PLS-DA) algorithm have been tested on three simulated data sets characterized by a varying degree of non-linearity: in all cases, a classification accuracy higher than 99% on external validation samples was achieved. Moreover, when also applied to a real data set (classification of rice varieties), characterized by a high extent of non-linearity, the proposed method provided an average correct classification rate of about 93% on the test set. By the preliminary results, showed in this paper, the performances of the proposed LW-PLS-DA approach have proved to be comparable and in some cases better than those obtained by other non-linear methods (k nearest neighbors, kernel-PLS-DA and, in the case of rice, counterpropagation neural networks).

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-KappaB by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-KappaB increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-KappaB pathway.

Monocytes and lymphocytes form a second wave of infiltrating blood leukocytes in areas of tissue injury. The mechanisms for monocyte accumulation at these sites are not completely understood. Recently, however, fragments from extracellular matrix proteins including collagen, elastin, and fibronectin have been shown to induce monocyte chemotaxis. In this report we demonstrate that chemotactic activity for human monocytes is expressed when a 120-kDa fragment containing the RGDS cell-binding peptide is released from intact fibronectin or from larger fibronectin fragments. Monocytes, either from mononuclear cell Ficoll-Hypaque preparations (10-20% monocytes, 89-90% lymphocytes) or from elutriation preparations (95% monocytes, 5% lymphocytes), but not lymphocytes, migrated toward 120-kDa fragment preparations (10(-7) M) in blind-end chambers when the cells were separated from the chemoattractant by a 5-micron pore polycarbonate filter either alone or overlying a 0.45-micron pore nitrocellulose filter. Neutrophils migrated toward zymosan-activated serum but not toward 10(-5)-10(-8) M concentrations of the 120-kDa fragment. Intact fibronectin had no chemotactic activity for human monocytes. Fibronectin was isolated from citrated human plasma by sequential gelatin-Sepharose affinity and DEAE ion-exchange chromatography in the presence of buffers containing 1 mM phenylmethylsulfonyl fluoride to prevent fragmentation. Controlled enzymatic digestion with thermolysin cleaved fibronectin into 30 kDa fibrin, 45 kDa collagen, and 150/160-kDa cell and heparin domains. Upon prolonged digestion, purified 150/160-kDa fragments were cleaved into 120-kDa cell and 30/40-kDa heparin-binding fragments. Even though the intact fibronectin molecule, the 150/160-kDa fragments, and the 120-kDa fragment, have cell binding activity for Chinese hamster ovary fibroblasts, only the 120-kDa fragment expressed chemotactic activity for human monocytes. Thus, the 120-kDa fibroblastic cell

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease.

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Dark Agouti (DA) rats are highly susceptible to induction of Th-l-mediated autoimmunity disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible rat strains in which disease is induced only with encephalitogen emulsified in complete Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph node cells derived from immunized DA rats and stimulated in vitro produce significantly more Interferon-γ (IFN-γ) than resistant Albino Oxford (AO) rats. However, cells derived from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells derived from EAE susceptible (AO × DA) F1rats induce clinical signs of disease in sublethally irradiated parental DA but not AO rats. The pathohistology of the target tissue in these recipients clearly demonstrated infiltration of mononuclear cells in both parental strains. However, the number of CD4+ cells was significantly higher and number of apoptotic cells significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in addition to higher IFN-γ and TNF-α production, resistance to early apoptosis of the invading cells in the target tissue possibly due to lack of downregulation by TGF-β leads to exceptional susceptibility to EAE in DA rats. PMID:11785669

DA-9601 (Stillen™) is a novel anti-peptic formulation prepared from the ethanol extracts of Artemisia asiatica possessing anti-oxidative, anti-allergic and anti-inflammatory activities. However, their effect on atopic dermatitis (AD) has not been studied yet. In this study, we report that topical application of DA-9601 suppressed house dust mite extract (Dermatophagoides farinae extract, DFE) and 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in BALB/c mice model. We established atopic dermatitis model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like lesions. DA-9601 reduced AD-like skin lesions based on ear thickness and histopathological analysis, and serum IgE levels. DA-9601 inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. In addition, DA-9601 suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears. Taken together, our results showed that topical application of DA-9601 exerts beneficial effects in animal model of AD, suggesting that DA-9601 might be a candidate for the treatment of AD.

Background/Aims DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Methods Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. Results The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. Conclusions DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway. PMID:27114435

Virtual reality simulators are increasingly used to gain robotic surgical skills. This study compared use of the da Vinci Surgical Skills Simulator (dVSSS) to the standard da Vinci (SdV) robot for skills acquisition in a prospective randomized study. Residents from urology, gynecology, and general surgery programs performed three virtual reality tasks (thread the ring, ring rail, and tubes) on the dvSSS. Participants were then randomized to one of the two study groups (dVSSS and SdV). Each participant then practiced on either the dVSSS or the SdV (depending on randomization) for 30 min per week over a 4-week time period. The dVSSS arm was not permitted to practice ring rail (due to no similar practice scenario available for the SdV group). Following 4 weeks of practice, participants performed the same three virtual reality tasks and the results were recorded and compared to baseline. Overall and percent improvement were recorded for all participants from pre-test to post-test. Two-way ANOVA analyses were used to compare the dVSSS and SdV groups and three tasks. Initially, 30 participants were identified and enrolled in the study. Randomization resulted in 15 participants in each arm. During the course of the study, four participants were unable to complete all tasks and practice sessions and were, therefore, excluded. This resulted in a total of 26 participants (15 in the dVSSS group and 11 in the SdV group) who completed the study. Overall total improvement score was found to be 23.23 and 23.48 for the SdV and dVSSS groups, respectively (p = 0.9245). The percent improvement was 60 and 47 % for the SdV and dVSSS groups respectively, which was a statistically significant difference between the two groups and three tasks. Practicing on the standard da Vinci is comparable to practicing on the da Vinci simulator for acquiring robotic surgical skills. In spite of several potential advantages, the dVSSS arm performed no better than the SdV arm in the final

Tristan da Cunha is a volcanic island in the South Atlantic close to the Mid-Atlantic Ridge. It is part of an area consisting of widely scattered seamounts and small islands at the western and youngest end of the aseismic Walvis Ridge. Tristan da Cunha together with the Walvis Ridge represents the classical example of a mantle plume track, because of the connection to the Cretaceous Etendeka flood basalt province in NW Namibia. The genesis of the island has so far remained enigmatic. It is hotly debated, if Tristan da Cunha sits actually above a deep mantle plume or if it is only originated by upwelling material from weak (leaky) fracture zones. It also has to be clarified if there are any indications for a plume-ridge interaction. Geochemical investigations have shown complex compositions of magmatic samples from Tristan da Cunha, which could be interpreted as a mixing of plume-derived melts and depleted upper mantle sources. To improve our understanding about the origin of Tristan and to test the mantle plume hypothesis, we deployed 24 broadband ocean-bottom seismometers and 2 seismological land stations around and on the island during an expedition in January 2012 with the German research vessel Maria S. Merian. After acquiring continuous seismological data for almost one year, the seismometers were recovered in early January 2013. We cross-correlated the arrival times of teleseismic P and PKP phases to perform a finite-frequency tomography of the upper mantle beneath the study area. Here we show the 3D mantle structure in terms of velocity variations: We do not image a "classical" plume-like structure directly beneath Tristan da Cunha, but we observe regions of low velocities at the edges of our array that we relate to local mantle upwelling from potentially deeper sources. Additionally we discuss local seismicity within the Tristan da Cunha region, which show processes along the nearby mid-ocean ridge and transform faults. Furthermore, the local seismicity

It was shown by immunofluorescence method that serum M68 and serum K43 from patients with autoimmune disease stain interphase nuclei and periphery of mitotic chromosomes of pig kidney cells. Western blotting reveals the polypeptide with mol. mass of 50 kDa in serum M68, and the polypeptide with mol. mass of 38 kDa in serum K43. In the nuclear protein matrix, the antibodies to protein with mol. mass of 38 kDa stained only nucleolar periphery, while the antibodies to the protein with mol. mass of 50 kDa stained both the nucleolar periphery and all the interphase nucleus. It shows that among all components of nuclear protein matrix (lamina, internuclear network, residual nucleoli) only nucleolar periphery contains the 38 kDa protein, while the 50 kDa protein is a part of residual nucleolar periphery and takes part in nuclear protein network formation. In the interphase cells, both proteins were in situ localized in the nuclei, but one of them with mol. mass of 50 kDa was in the form of small clearly outlined granules, while the other (38 kDa) was in the form of small bright granules against the background of diffusely stained nuclei. Both proteins were also revealed as continuous ring around nucleolar periphery. During all mitotic stages, the 50 kDa protein was seen on the chromosomal periphery as a cover, and the 38 kDa protein formed separate fragments and granules around them. After nuclear and chromosome decondensation induced by hypotonic treatment, both antibodies stain interphase nuclei in diffuse manner, but in mitotic cells they stained the surface of the swollen chromosomes. The polypeptide with mol. mass of 50 kDa maintained strong connection with chromosome periphery both in norm and under condition of decondensation induced by hypotonic treatment and at subsequent recondensation in isotonic medium. In contrast, the protein with mol. mass of 38 kDa partially lost the contact with a chromosome during recondensation appearing also in the form of granules in

Dialogs with the previous article establishing a comparative analysis between the political acceptance present in the reactionary speech of Dom Jose Mauricio da Rocha and in the monarchist words of Joaquim Nabuco. (PA)

For several years the PanDA Workload Management System has been the basis for distributed production and analysis for the ATLAS experiment at the LHC. Since the start of data taking PanDA usage has ramped up steadily, typically exceeding 500k completed jobs/day by June 2011. The associated monitoring data volume has been rising as well, to levels that present a new set of challenges in the areas of database scalability and monitoring system performance and efficiency. These challenges are being met with a R&D effort aimed at implementing a scalable and efficient monitoring data storage based on a noSQL solution (Cassandra). We present our motivations for using this technology, as well as data design and the techniques used for efficient indexing of the data. We also discuss the hardware requirements as they were determined by testing with actual data and realistic loads.

Haemophilus paragallinarum is the causal agent of infectious coryza, an economically important disease for the poultry industry. This bacterium secreted proteins of 25-110 kDa during its growth in brain heart infusion, tryptic soy broth, or Luria-Bertani glucose phosphate media, all lacking serum. Some of these proteins were recognized by sera from chickens experimentally infected with H. paragallinarum. A 110-kDa protein was recognized by a serum pool from convalescent-phase pigs naturally infected with Actinobacillus pleuropneumoniae, and also by a rabbit polyclonal serum against Apx I as well as a rabbit serum against Mannheimia haemolytica leukotoxin, suggesting the presence of an RTX-like protein in H. paragallinarum. H. paragallinarum secreted proteins could be important immunogens in the control of infectious coryza.

Incubation of a 90-kDa ferritin repressor protein (FRP) with small amounts of radiolabeled hemin resulted in the formation of a strong interaction between the two that was stable to SDS/PAGE. Of seven other proteins tested individually, only apohemopexin and bovine serum albumin showed similar crosslinking ability, albeit to a much lower extent. ({sup 14}C)Hemin specifically crosslinked to FRP in the presence of a 50-fold excess of total wheat germ proteins. Inclusion of catalase did not prevent the reaction of hemin with FRP, suggesting that H{sub 2}O{sub 2} is not involved. The subsequent addition of a stoichiometric amount of apohemopexin did not reverse the reaction. Exhaustive digestion of the complex with Staphylococcus aureus V8 protease produced a major labeled peptide of 17 kDa. These results show the existence of a highly specific, uniquely reactive hemin binding site on FRP.

We received for examination a small colection of ticks captured in the National Park of the Serra da Canastra (MG), between 1979 and 1980. The authors demonstrated the existence of a broad co-accomodation of Amblyomma pseudoconcolor on Edentata of the family Dasypodidae, being Dasypodini the tribe more adjusted to this infestation. In conformity to the Figs 1 and 2, Dasypodini are probably the real hosts of A. pseudoconcolor and also the oldest hosts. For the first time, A. pseudoconcolor is also recorded on Cabassous tatouay, C. unicinctus, Priodontes maximus and Euphractus sexcincuts. Also for the first time A. pseudoconcolor and Amblyomma calcaratum were recorded in the State of Minas Gerais. The ectoparasites are deposited in the "Departamento de Parasitologia da Universidade Federal de Minas Gerais, Brasil".

We report the results of a simultaneous analysis of the Chandra and XMM- Newton data on the pulsar wind nebula DA 495 and its central object, J1952.2+2925, which is presumably a pulsar. The J1952.2+2925 pure thermal spectrum can be equally well described either by the blackbody model with a temperature of 215 eV and an emitting area radius of 0.6 km or magnetized neutron star atmosphere models with temperatures of 80-90 eV. We also used the high temporal resolution XMM-Newton/EPIC-pn data to search for pulsations from J1952.2+2925. No pulsations were found so we set an upper limit for the pulsed fraction which is 40%. Using of the interstellar absorption-distance relation allowed us to estimate the distance to DA 495, which lies between 1 and 5 kpc.

Downstream regulatory element antagonist modulator (DREAM) is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. Previous work has shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger 3 (NCX3) in cerebellar granular neurons to control Ca2+ homeostasis and survival of these neurons. To achieve a global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Here we show that DREAM regulates the expression of the midline 1 (Mid1) gene early after birth. As a consequence, daDREAM mice exhibit a significant shortening of the rostro-caudal axis of the cerebellum and a delay in neuromotor development early after birth. Our results indicate a role for DREAM in cerebellar function. PMID:22563308

The discoloration of ancient paper, due to the development of oxidized groups acting as chromophores in its chief component, cellulose, is responsible for severe visual degradation in ancient artifacts. By adopting a non-destructive approach based on the combination of optical reflectance measurements and time-dependent density functional theory ab-initio calculations, we describe and quantify the chromophores affecting Leonardo da Vinci's iconic self-portrait. Their relative concentrations are very similar to those measured in modern and ancient samples aged in humid environments. This analysis quantifies the present level of optical degradation of the Leonardo da Vinci's self-portrait which, compared with future measurements, will assess its degradation rate. This is a fundamental information in order to plan appropriate conservation strategies.

Pentacyclic lactam acceptor unit TPTI invented by our group is proved to be a good building block for efficient D-A copolymers used in organic solar cells. Here, two D-A copolymers PBTTPTI and PTTTPTI are developed by copolymerizing TPTI with 2,2'-bithiophene (BT) or thieno[3,2-b]thiophene (TT). PBTTPTI and PTTTPTI exhibit good solubility and strong interchain π-π interaction even in dilute solution. They possess deep HOMO levels (ca. -5.3 eV), partial crystallinity, and good hole mobilities. Blending with PC71 BM, PBTTPTI and PTTTPTI give decent power conversion efficiencies (PCE) up to 6.83% and 5.86%, with outstanding fill factors (FF) of 74.3% and 71.3%, respectively.

Attention is given to model calculations of the far- and extreme-UV line spectra of highly ionized Fe species (Fe IV, Fe V, and Fe VI) for hot high-gravity H-rich stars. A spectral analysis of 31 hr of exposure of the DA white dwarf Feige 24 with IUE in the echelle mode reveals the presence of Fe with an abundance relative to H by number of (5-10) x 10 exp -6 with an uncertainty dominated by the determination of stellar parameters. An analysis of IUE data from the white dwarf G191 B2B results in a similar Fe abundance if this star shares similar atmospheric parameters (Teff, g) with Feige 24. Fe is thus the second most abundant photospheric element in hot DA white dwarfs.

Camera positioning is critical for all telerobotic surgical systems. Inadequate visualization of the remote site can lead to serious errors that can jeopardize the patient. An autonomous camera algorithm has been developed on a medical robot (da Vinci) simulator. It is found to be robust in key scenarios of operation. This system behaves with predictable and expected actions for the camera arm with respect to the tool positions. The implementation of this system is described herein. The simulation closely models the methodology needed to implement autonomous camera control in a real hardware system. The camera control algorithm follows three rules: (1) keep the view centered on the tools, (2) keep the zoom level optimized such that the tools never leave the field of view, and (3) avoid unnecessary movement of the camera that may distract/disorient the surgeon. Our future work will apply this algorithm to the real da Vinci hardware.

Nanotubes are generally not perfectly straight cylinders and the local curvature can influence transport properties. As shown by da Costa [1], charged particles moving on a curved surface experience an effective potential which modifies their dynamics. In this paper, we solve a one-electron Schrödinger equation in a distorted nanotube with open boundary conditions. We find that the deformations may open bandgaps suggesting their use in the design of nanotube- based electronic devices.

otherwise. Unless DA can cause this perception to be changed, these sections of the OER are likely to become meaning- less due to a self -fulfilling...first of these measures revolves around an individual’s self -esteem and his perceived importance of the ratings received on the 0ER. The hypothesis to...be tested by this measure is that individuals with high self -esteem place less importance on absolute scores and more importance on actual job

The authors report 22.2 GHz observations of the quasar 0552+398 (DA 193). The data are used to refine the source structure model and magnetic field estimate previously reported by Spangler and colleagues in 1983. The source is found to be more compact and the magnetic field to be weaker than indicated by the previous observations. It is suggested that the object may be considered a highly compact, "naked core" object.

The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on salsolinol (SAL)-induced prolactin (PRL) release in goats. The PRL-releasing response to an intravenous (i.v.) injection of SAL was examined after treatment with augmentation of central DA using carbidopa (carbi) and L-dopa in male goats under 8-h (8 h light, 16 h dark) or 16-h (16 h light, 8 h dark) photoperiod conditions. The carbi and L-dopa treatments reduced basal PRL concentrations in the 16-h photoperiod group (P DA blunts the SAL-induced release of PRL in male goats, regardless of the photoperiod, which suggests that both SAL and DA are involved in regulating the secretion of PRL in goats.

The handedness of Leonardo da Vinci is controversial. Although there is little doubt that many of his well-attributed drawings were drawn with the left hand, the hatch marks of the shading going downwards from left to right, it is not clear that he was a natural left-hander, there being some suggestion that he may have become left-handed as the…

Rozitis et al. recently reported that near-Earth asteroid (29075) 1950 DA, whose bulk density ranges from 1.0 g cm{sup –3} to 2.4 g cm{sup –3}, is a rubble pile and requires a cohesive strength of at least 44-76 Pa to keep from failing due to its fast spin period. Since their technique for giving failure conditions required the averaged stress over the whole volume, it discarded information about the asteroid's failure mode and internal stress condition. This paper develops a finite element model and revisits the stress and failure analysis of 1950 DA. For the modeling, we do not consider material hardening and softening. Under the assumption of an associated flow rule and uniform material distribution, we identify the deformation process of 1950 DA when its constant cohesion reaches the lowest value that keeps its current shape. The results show that to avoid structural failure the internal core requires a cohesive strength of at least 75-85 Pa. It suggests that for the failure mode of this body, the internal core first fails structurally, followed by the surface region. This implies that if cohesion is constant over the whole volume, the equatorial ridge of 1950 DA results from a material flow going outward along the equatorial plane in the internal core, but not from a landslide as has been hypothesized. This has additional implications for the likely density of the interior of the body.

Background Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. Methods Using western blot, we measured the levels of the 60 kDa heat shock protein (Hsp60) and of the inducible 71 kDa member of the Hsp70 family (Hsp71) in lymphocytes and the presence of antibodies against these hsps in plasma of 29 pediatric patients with ITP before the treatment and in 6 other patients before and after treatment. Results Interestingly only one out of 29 patients showed detectable Hsp60 in lymphocytes while this heat shock protein was detected in the 30 control children. Hsp71 levels were slightly lower in lymphocytes of patients with ITP than in controls (1567.8 ± 753.2 via 1763.2 ± 641.8 integrated optical density (IOD) units). There was a small increase of Hsp71 after recovery from ITP. The titers of plasma antibodies against Hsp60 and Hsp71 were also examined. Antibodies against Hsp71 were more common in ITP patients (15/29) than in control children (5/30). The titer of anti-Hsp71 was also higher in children patients with ITP. The prevalence of ITP children with antibodies against Hsp71 (51.7%) was as high as those with antibodies against platelet membrane glycoproteins (58.3%). Conclusions In summary, pediatric patients with ITP showed no detectable expression of Hsp60 in lymphocytes and a high prevalence of antibody against Hsp71 in plasma. These changes add to our understanding of the pathogenesis of ITP and may be important for the diagnosis, prognosis and treatment of ITP. PMID:15070425

The [123I]ioflupane—a dopamine transporter radioligand—SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X–associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases. PMID:24744729

... three times per week in sessions lasting between three and five hours. Kidney transplantation is the... of DaVita and DSI's head-to-head competition in these markets, indicates that the combined firm...

Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or γ-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development.

A novel engraving machine (NUT-1A) is presented, in which fully digital controlled AC system based on DEC4DA was used to improve the machining precision and sensitivity. This engraving machine was constructed around AC servo motor with encoder, controlled by a servo motor control card - DEC4DA. As the upper unit of AC servo motor, DEC4DA was a numerical control generator, which received pulses form CPU by ISA bus, and these pulses were amplified and converted to drive AC servo actuator. This novel engraving machine can achieve a higher positioning accuracy of +/-0.01mm and positioning repetition of +/-0.005mm, and its resolution is 0.001mm/0.0001mm. Moreover, because of multi-closed loops were used in the system, the steady and transient performances are more excellent. This system ensures a much quicker current regulation in closed-loop operation, of acceleration and braking in both directions, as well as stable speed characteristics. Amplifier boards are protected against excessive current, excessive temperature and short circuiting of the motor supply cables.

Summary: Gene Ontology (GO) semantic similarity measures are being used for biological knowledge discovery based on GO annotations by integrating biological information contained in the GO structure into data analyses. To empower users to quickly compute, manipulate and explore these measures, we introduce A-DaGO-Fun (ADaptable Gene Ontology semantic similarity-based Functional analysis). It is a portable software package integrating all known GO information content-based semantic similarity measures and relevant biological applications associated with these measures. A-DaGO-Fun has the advantage not only of handling datasets from the current high-throughput genome-wide applications, but also allowing users to choose the most relevant semantic similarity approach for their biological applications and to adapt a given module to their needs. Availability and implementation: A-DaGO-Fun is freely available to the research community at http://web.cbio.uct.ac.za/ITGOM/adagofun. It is implemented in Linux using Python under free software (GNU General Public Licence). Contact: gmazandu@cbio.uct.ac.za or Nicola.Mulder@uct.ac.za Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26476781

John Chalmers DaCosta was an influential chairman and the first Samuel D. Gross Professor of Surgery at Jefferson Medical College in Philadelphia. He was well known throughout the field as a skilled surgeon, passionate speaker, and exceptional writer. In addition to countless accomplishments during his career, DaCosta was deeply dedicated to the preservation and commemoration of surgical history. This ideology was exemplified when he set out on a mission to recover the old wooden operating table used by many of his iconic mentors including Samuel D. Gross, Joseph Pancoast, and William W. Keen. This table was originally used for surgical demonstrations and anatomy lessons in a lecture room of the Ely Building and later in the great amphitheater of the Jefferson Sansom Street Hospital. It was found forgotten in the basement of the College Building and was promptly refurbished, donned with dedicatory plaques, and returned to its honored position in the medical college. Dr. DaCosta also contributed a detailed article recalling the history of the table and the notable leaders in surgery who taught and practiced on its surface. The old table currently stands proudly in the entranceway of the Department of Surgery where it will remain as a cherished symbol of the early beginnings of surgical practice and education.

Surface quality of advanced superalloys after machining is one of the major issues in the aerospace industry because it directly affects service characteristics of the machined part. Tool life of cemented carbide inserts with the TiAlN coating during machining of direct aged DA 718 alloys under roughing and finishing conditions has been under study. The defect origin on the surface of the machined part was investigated. Metallographic observations of the DA 718 were made using optical metallography and SEM/EDS. To find out the origins of surface defect formation, the morphology of machined parts and cross sections of the machined surfaces have been investigated. Two major categories of defects were detected on the surface of the machined part: cracks and tears. The origin of the cracks on the machined surface is related to shearing of the primary complex TiC/NbC carbide revealed in a structure of DA 718 alloy. At the same time, Nb-rich regions of the primary complex carbide interact with the environment (oxygen from air) during machining with further formation of low strength oxide layer on the surface, forming tears.

Low molecular weight components of shark cartilage are reported to have anti-tumor as well as immuno-stimulating effects. Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that have a key role in establishment of anti-cancer immune response. In this study, the effect of 14 kDa protein from shark cartilage was investigated on stimulation and maturation of dendritic cells. The isolated 14 kDa protein from shark cartilage extract was added to DCs medium during overnight culture and their maturation and T cells stimulation potential was investigated. The majority of shark-cartilage-treated DCs expressed higher levels of maturation markers and were more effective in stimulation of allogenic T cells compared with non-treated DCs (p Da protein can potentially be used in DC-mediated T-cells stimulation and induction of desirable immune responses in clinical trials such as cancer immunotherapy. However, further studies are required to examine this proposal.

This article describes a free and open-source data analysis utility designed for fast online feedback during serial X-ray diffraction and scattering experiments: OnDA (online data analysis). Three complete real-time monitors for common types of serial X-ray imaging experiments are presented. These monitors are capable of providing the essential information required for quick decision making in the face of extreme rates of data collection. In addition, a set of modules, functions and algorithms that allow developers to modify the provided monitors or develop new ones are provided. The emphasis here is on simple, modular and scalable code that is based on open-source libraries and protocols. OnDA monitors have already proven to be invaluable tools in several experiments, especially for scoring and monitoring of diffraction data during serial crystallography experiments at both free-electron laser and synchrotron facilities. It is felt that in the future the kind of fast feedback that OnDA monitors provide will help researchers to deal with the expected very high throughput data flow at next-generation facilities such as the European X-ray free-electron laser. PMID:27275150

A 155-kDa proteinase inhibitor, pacifastin, from plasma of the freshwater crayfish, Pacifastacus leniusculus, was found to be composed of two covalently linked subunits. The two subunits are encoded by two different mRNAs, which were cloned and sequenced. The heavy chain of pacifastin (105 kDa) is related to transferrins, containing three transferrin lobes, two of which seem to be active for iron binding. The light chain of pacifastin (44 kDa) is the inhibitory subunit, and has nine cysteine-rich inhibitory domains that are homologous to each other and to low molecular weight proteinase inhibitors isolated from the grasshopper, Locusta migratoria. The nine light chain domains and the Locusta inhibitors share a characteristic cysteine array (Cys-Xaa9–12-Cys-Xaa2-Cys-Xaa-Cys-Xaa6–8-Cys-Xaa4-Cys) distinct from any described proteinase inhibitor family, suggesting that they constitute a new family of proteinase inhibitors. Pacifastin is the first known protein that has combined properties of a transferrin-like molecule and a proteinase inhibitor. PMID:9192625

Background/Aims Post-operative ileus (POI) is a common complication of abdominal surgery. DA-9701, an extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that also alleviates visceral pain. The aim of this study was to investigate whether DA-9701 can ameliorate POI in rats. Methods A total of 32 rats were divided into 4 groups: no surgery/no medication (NSNM), no surgery/medication (NSM), surgery/no medication (SNM), and surgery/medication (SM). Gastrointestinal transit (GIT), which is assessed by migration of charcoal, and cumulative stool weight were measured at 24 hours after surgery. Results GIT was significantly more delayed in the SNM group than in the other groups (SNM vs NSNM, P < 0.001; SNM vs NSM, P < 0.001; SNM vs SM, P = 0.005). Cumulative stool weight in that group was also lower than in the no surgery groups (SNM vs NSNM, P = 0.007; SNM vs NSM, P = 0.033), and there was no significant difference between the SM group and the no surgery groups (SM vs NSM, P = 0.703; SM vs NSNM, P = 0.347). Conclusion DA-9701 can ameliorate POI by reducing delayed GIT and improving defecation in a rat model of POI. PMID:27832682

Replication protein A (RPA) is a heterotrimeric (70, 32 and 14 kDa subunits), single-stranded DNA-binding protein required for cellular DNA metabolism. All subunits of RPA are essential for life, but the specific functions of the 32 and 14 kDa subunits remains unknown. The 32 kDa subunit (RPA2) has multiple domains, but only the central DNA-binding domain (called DBD D) is essential for life in Saccharomyces cerevisiae. To define the essential function(s) of RPA2 in S. cerevisiae, a series of site-directed mutant forms of DBD D were generated. These mutant constructs were then characterized in vitro and in vivo. The mutations had minimal effects on the overall structure and activity of the RPA complex. However, several mutants were shown to disrupt crosslinking of RPA2 to DNA and to dramatically lower the DNA-binding affinity of a RPA2-containing subcomplex. When introduced into S. cerevisiae, all DBD D mutants were viable and supported normal growth rates and DNA replication. These findings indicate that RPA2–DNA interactions are not essential for viability and growth in S. cerevisiae. We conclude that DNA-binding activity of RPA2 is dispensable in yeast and that the essential function of DBD D is intra- and/or inter-protein interactions. PMID:19244309

Robotic surgery is a reality. In order to to understand how new robots work is interesting to know the history of ancient (see part i) and modern robotics. The desire to design automatic machines imitating humans continued for more than 4000 years. Archytas of Tarentum (at around 400 a.C.), Heron of Alexandria, Hsieh-Fec, Al-Jazari, Bacon, Turriano, Leonardo da Vinci, Vaucanson o von Kempelen were robot inventors. At 1942 Asimov published the three robotics laws. Mechanics, electronics and informatics advances at XXth century developed robots to be able to do very complex self governing works. At 1985 the robot PUMA 560 was employed to introduce a needle inside the brain. Later on, they were designed surgical robots like World First, Robodoc, Gaspar o Acrobot, Zeus, AESOP, Probot o PAKI-RCP. At 2000 the FDA approved the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale, CA, USA), a very sophisticated robot to assist surgeons. Currently urological procedures like prostatectomy, cystectomy and nephrectomy are performed with the da Vinci, so urology has become a very suitable speciality to robotic surgery.

Lymphocytic hypophysitis is part of the spectrum of organ-specific autoimmune diseases, and although its histopathology is well documented, its pathogenesis is unclear. Serum autoantibodies directed against a 49-kDa cytosolic protein are detected by immunoblotting in 70% of patients with biopsy-proven lymphocytic hypophysitis. Here we report the purification and identification of this first target autoantigen in lymphocytic hypophysitis. The autoantigen has a molecular mass of 49 kDa, a cytosolic localization, and a ubiquitous tissue distribution. The 49-kDa protein was purified from monkey brain and human placental cytosol. Limited amino acid sequencing after proteolytic digestion of the human placental protein showed identity with alpha-enolase. The identification was confirmed using sera from patients with pituitary autoimmunity, which strongly reacted with recombinant human alpha-enolase and yeast enolase, but not with rabbit muscle beta- enolase. This indicates that the immunoreactive epitopes are largely conserved from yeast to human, but are not present in beta-enolase. alpha-Enolase autoantibodies are not specific to pituitary autoimmune disease and have been reported in other autoimmune diseases. However, this study is the first to indicate a role for alpha-enolase as an autoantigen in lymphocytic hypophysitis.

QuEChERS procedure and acetonitrile extraction, oscillation and ultrasonic procedure followed by GC-MS and LC-MS/MS (QqQ) detections were established for determination of diethyl aminoethyl hexanoate (DA-6) residues in pakchoi, cotton leaf, cotton seed and soil. At concentration levels of 0.005-1 mg kg(-1), recoveries were in the range of 80.5%-103.3%, with a RSD less than 14.2%. The LOQs of methods were 0.005, 0.003, 0.005 and 0.001 mg kg(-1) for the pakchoi, cotton leaf, soil and cotton seed samples, respectively. DA-6 was applied in supervised field trials at GAP conditions to pakchoi and cotton. It was found that the dissipation half-lives of DA-6 were 5.4-8.2 days and 1.1-2.2 days and 1.5-1.9 days in cotton crop, pakchoi and soil respectively. At harvest, no detectable residues (

It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.

... 32 National Defense 3 2012-07-01 2009-07-01 true Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016...

... 32 National Defense 3 2010-07-01 2010-07-01 true Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016...

... 32 National Defense 3 2013-07-01 2013-07-01 false Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016...

... 32 National Defense 3 2011-07-01 2009-07-01 true Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016...

... 32 National Defense 3 2014-07-01 2014-07-01 false Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016...

A new copolymer PIDTDTQx based on indacenodithiophene and quinoxaline is synthesized and characterized. The correlation between the D/A ratio, mobility, and photovoltaic properties, as well as morphology of the D/A blend based on a PIDTDTQx:PC(70) BM system is investigated. The power conversion efficiency of the polymer solar cells based on PIDTDTQx/PC(70) BM (1:4, w/w) reaches 7.51%.

The TGACGTCA (CRE) motif required for function by a number of cellular (somatostatin, enkephalin, alpha-human chorionic gonadotropin) and viral (Ad5 E1A-inducible, HTLV-1 TAX-inducible) genes is the site of interaction of multiple sequence-specific complexes. A protocol has been developed for the fractionation and purification of these activities. We report here the purification from HeLa nuclear extracts of a novel 120-kDa polypeptide which by Southwestern blots, gel retardation, and UV cross-linking assays displays CRE-specific binding. The CRE-affinity purified 120-kDa protein displays properties distinct from those of the 43-kDa CREB/ATF polypeptide. The 120-kDa protein is readily phosphorylated in vitro by protein kinase C but not by protein kinase A, suggesting that this molecule may mediate cellular signals distinct from the cAMP-responsive pathway. In vitro transcription-complementation assays utilizing the purified 120-kDa protein failed to transactivate the cAMP-responsive somatostatin promoter suggesting that the mode of action of this 120-kDa polypeptide may require an activation step distinct from the cAMP-signaling pathway.

This study was aimed to explore the clinical efficacy and toxicity of idarubicin (IA regimen) and daunoru-bicin combined with cytarabine (DA regimen) for treating aged patients with AML as induction chemotherapy. The clinical data of 60 newly diagnosed AML aged patients treated with IA or DA regimen were analyzed retrospectively. IA regimen group included 22 patients (8 male and 14 females with median age of 66 yrs), while the DA regimen group included 38 patients (20 males and 18 females with median age of 64 yrs). The complete remission rate, total effective rate and adverse effects after one chemotherapy course were compared. The results showed that the CR rate in IA regimen group was 63.63%, which was significantly higer than that in DA regimen group (31.58%) (P < 0.05). The total effective rate was 63.63% and 36.84% respectively in IA and DA regimen groups, there was significant difference between the two groups (P < 0.05). Both the hematological and non-hematological adverse effects were observed and no difference was found in the two regimen groups, neither in myelosupression (P > 0.05), the major hematological adverse effects, nor in non-hematological adverse effects (P > 0.05). It is concluded that for aged AML patients, IA regimen can achieve a higher CR rate and higher total effective rate than that in DA regimen without increase of adverse effects after one induction chemotherapy course.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDL receptor (LDLR) at the cell surface and reroutes the internalized LDLR to intracellular degradation. In this study, we have shown that PCSK9-mediated degradation of the full-length 160 kDa LDLR generates a 17 kDa C-terminal LDLR fragment. This fragment was not generated from mutant LDLRs resistant to PCSK9-mediated degradation or when degradation was prevented by chemicals such as ammonium chloride or the cysteine cathepsin inhibitor E64d. The observation that the 17 kDa fragment was only detected when the cells were cultured in the presence of the γ-secretase inhibitor DAPT indicates that this 17 kDa fragment undergoes γ-secretase cleavage within the transmembrane domain. The failure to detect the complementary 143 kDa ectodomain fragment is likely to be due to its rapid degradation in the endosomal lumen. The 17 kDa C-terminal LDLR fragment was also generated from a Class 5 mutant LDLR undergoing intracellular degradation. Thus, one may speculate that an LDLR with bound PCSK9 and a Class 5 LDLR with bound LDL are degraded by a similar mechanism that could involve ectodomain cleavage in the endosome.

Bacillus thuringiensis subsp. aizawai strain HD133, known by its effectiveness against Spodoptera species, produces many insecticidal proteins including Cry1Ab, Cry1Ca and Cry1Da. In the present study, the insecticidal activity of Cry1Da against Spodoptera littoralis was investigated. It showed toxicity with an LC(50) of 224.4 ng/cm(2) with 95% confidence limits of (178.61-270.19) and an LC(90) of 467.77 ng/cm(2) with 95% confidence limits of (392.89-542.65). The midgut histopathology of Cry1Da fed larvae showed vesicle formation in the apical region, vacuolization and destruction of epithelial cells. Biotinylated-activated Cry1Da toxin bound protein of about 65 kDa on blots of S. littoralis brush border membrane preparations. This putative receptor differs in molecular size from those recognized by Cry1C and Vip3A which are active against this polyphagous insect. This difference in midgut receptors strongly supports the use of Cry1Da as insecticidal agent, particularly in case of Cry and/or Vip-resistance management.

We present an improved spectroscopic and photometric analysis of hydrogen-line DA white dwarfs from the Sloan Digital Sky Survey Data Release 4 (SDSS DR4) based on model atmospheres that include improved Stark broadening profiles with non-ideal gas effects. We also perform a careful visual inspection of all spectroscopic fits with high signal-to-noise ratios (S/Ns > 12) and present improved atmospheric parameters (T{sub eff} and log g) for each white dwarf. Through a comparison of spectroscopic and photometric temperatures, we report the discovery of 35 DA+DB/DC double degenerate candidates and two helium-rich DA stars. We also determine that a cutoff at S/N = 15 optimizes the size and quality of the sample for computing the mean mass of DA white dwarfs, for which we report a value of 0.613 M{sub sun}. We compare our results to previous analyses of the SDSS DR4 and find a good agreement if we account for the shift produced by the improved Stark profiles. Finally, the properties of DA white dwarfs in the SDSS are weighed against those of the Villanova White Dwarf Catalog sample of Gianninas et al. We find systematically lower masses (by about 3% on average), a difference that we trace back to the data reduction procedure of the SDSS. We conclude that a better understanding of these differences will be important to determine the absolute temperature scale and mean mass of DA white dwarfs.

DA-8159, a selective inhibitor of phosphodiesterase type 5, was developed as a new drug for erectile dysfunction. The effect of DA-8159 on the electroretinogram (ERG) and the retinal histopathology were evaluated in rabbits. The ERG was performed prior to, and 1 and 5 hr after DA-8159 (5 to 30 mg/kg) administration. The plasma concentration of DA-8159 was determined at each time point, and retinal microscopic examination was also performed. There was no statistically significant ERG change at any dose or at any time. Though the 30 Hz flicker showed a prolongation of the implicit time at 5 hr after the administration of either DA-8159 15 mg or 30 mg/kg (p<0.05), but concurrent amplitude decreases were not statistically significant. At a dose of 5 mg/kg, no test drug was detected in the blood after either 1 or 5 hr. At either 15 mg/kg or 30 mg/kg, there was a dose-dependent increase in the blood concentration after 1 hr of drug administration, which decreased with time. In light and electron microscopic examinations of the retina, there was no remarkable change at any dose. These results suggest DA-8159 has a low risk potential to the retina, but further evaluation on the visual functions in human is needed. PMID:15308852

On UT 2013 February 15, the elongated 20x40 meter near-Earth asteroid 2012 DA14 made a close flyby of the Earth at a distance of approximately 27,000 km or 4 Earth-radii. This passage was inside the orbital distance of geosynchronous satellites and close to the Earth's Roche limit. This close encounter was unprecedented in our advance knowledge of the incoming trajectory, thereby allowing us to forge a detailed coordinated plan for observation and testing of physical models predicting tidal effects near our planet's Roche limit. Predicted outcomes of such close encounters include tidal disruption, changes in rotation state, and mass loss or mass redistribution due to seismic shaking. Each of these effects sensitively depend on how tidal energy is dissipated in the interior of the asteroid: a rubble pile will dissipate tidal energy differently than a solid or partially fractured monolith. The internal properties of asteroids in general and particularly those in the size range of 2012 DA14 are largely unknown. This encounter represents one of the first ever opportunities to observationally test models of the interior structure of small planetary bodies. We will present the results of a large multi-observatory campaign focused on 2012 DA14. This campaign includes data from shortly after discovery in 2012 and surrounding the close approach of the asteroid in February of 2013. These data were collected with over a dozen telescopes worldwide, ranging in aperture from 1m to 8m and include major facilities in Chile, Australia, New Zealand, South Africa, Israel, Hawaii, Arizona, New Mexico, and the Canary Islands. We will highlight the outcome of pre- and post-flyby visible-wavelength photometric and spectroscopic observations. This will include clear evidence that 2012 DA14 is now in a non-principal axis rotation state, requiring a multi-periodic tumbling model to fit its post-flyby rotational light curve. Such a complex rotation state is consistent with models for the

Data Assimilation techniques are essential elements in state-of-the-art development of models and their optimization with data in the field of groundwater, surface water and soil systems. They are essential tools in calibration of complex modelling systems and improvement of model forecasts. The OpenDA is a new and generic open source data assimilation environment for application to a choice of physical process models, applied to case dependent domains. OpenDA was introduced recently when the developers of Costa, an open-source TU Delft project [http://www.costapse.org; Van Velzen and Verlaan; 2007] and those of the DATools from the former WL|Delft Hydraulics [El Serafy et al 2007; Weerts et al. 2009] decided to join forces. OpenDA makes use of a set of interfaces that describe the interaction between models, observations and data assimilation algorithms. It focuses on flexible applications in portable systems for modelling geophysical processes. It provides a generic interfacing protocol that allows combination of the implemented data assimilation techniques with, in principle, any time-stepping model duscribing a process(atmospheric processes, 3D circulation, 2D water level, sea surface temperature, soil systems, groundwater etc.). Presently, OpenDA features filtering techniques and calibration techniques. The presentation will give an overview of the OpenDA and the results of some of its practical applications. Application of data assimilation in portable operational forecasting systems—the DATools assimilation environment, El Serafy G.Y., H. Gerritsen, S. Hummel, A. H. Weerts, A.E. Mynett and M. Tanaka (2007), Journal of Ocean Dynamics, DOI 10.1007/s10236-007-0124-3, pp.485-499. COSTA a problem solving environment for data assimilation applied for hydrodynamical modelling, Van Velzen and Verlaan (2007), Meteorologische Zeitschrift, Volume 16, Number 6, December 2007 , pp. 777-793(17). Application of generic data assimilation tools (DATools) for flood

Myoblast surface proteins with binding activity toward the N-terminal 29-kDa fragment of fibronectin were identified by two different experimental techniques: one involves radioiodination of the cell surface proteins, followed by solubilization with Triton X-100 and affinity purification on a Sepharose column conjugated with the 29-kDa fragment, and the other involves cross-linking of the 29-kDa fragment to the cells metabolically labeled with [35S]methionine, followed by immunoprecipitation with anti-29-kDa IgG. Both approaches revealed that primary cultures of chick myoblasts contain the 66- and 48-kDa proteins that bind to the 29-kDa fragment. These binding proteins were then purified to apparent homogeneity by two successive chromatographies of the solubilized extracts of 12-day-old embryonic muscle on wheat germ agglutinin-agarose and 29-kDa fragment-Sepharose columns. However, the 48-kDa protein was found to be derived from contaminating fibroblasts upon immunoblot analysis of the myogenic cell lines, rat L8E63 and mouse C2A3, and cultured fibroblasts using the antibody raised against the 66-kDa protein. Anti-66-kDa IgG inhibited the binding of the 125I-29-kDa protein to the primary culture of myoblasts in a dose-dependent manner. On the other hand, the same antibody showed little or no effect on the initial binding of 125I-fibronectin to the cell surface, but dramatically inhibited its incorporation into deoxycholate-insoluble matrices. Furthermore, Fab fragments of anti-66-kDa IgG completely blocked the incorporation of fluoresceinated fibronectin into matrices but not its binding to the cell surface. These results suggest that fibronectin matrix assembly is mediated at least in part by the interaction of the 66-kDa protein with the N-terminal type I domain of fibronectin.

In this work, we analyzed the kinetics of anti-Trichinella spiralis newborn larva (NBL) antibodies (Ab) and the antigenic recognition pattern of NBL proteins and its dose effects. Wistar rats were infected with 0, 700, 2000, 4000 and 8000 muscle larvae (ML) and bled at different time intervals up to day 31 post infection (p.i.). Ab production was higher with 2000 ML dose and decreased with 8000, 4000 and 700 ML. Abs were not detected until day 10, peaked on day 14 for the 2000 ML dose and on day 19 for the other doses and thereafter declined slowly from 19 to 31 days p.i. In contrast, Abs to ML increased from day 10, peaked on day 19 and remained high until the end of the study. Abs bound strongly at least to three NBL components of 188, 205 and 49 kDa. NBL antigen of 188 and 205 kDa were recognized 10-26 days p.i. and that of 49 kDa from day 10 to day 31 p.i. A weak recognition towards antigens of 52, 54, 62 and 83 kDa was also observed during the infection. An early recognition of 31, 43, 45, 55, 68 and 85 kDa ML antigens was observed whereas the response to those of 43, 45, 48, 60, 64 and 97 kDa (described previously as TSL-1 antigens) occurred late in the infection. A follow-up of antigen recognition up to day 61 with the optimal immunization dose (2000 ML) evidenced a decline of Ab production to the 49 kDa NBL antigen 42 days p.i., which suggested antigenic differences with the previously reported 43 kDa ML antigen strongly recognized late in the infection. To analyze the stage-specificity of the 49 kDa NBL antigen, polyclonal antibodies (PoAb) were obtained in rats immunized with 49 kDa NBL antigen. PoAb reacted strongly with the 49 kDa NBL component in NBL total soluble extract but no reactivity was observed with soluble antigen of the other T. spiralis stages. Albeit with less intensity, the 49 kDa component was also recognized by PoAb together with other antigens of 53, 97 and 107 kDa, in NBL excretory-secretory products (NBL-ESP). Thus, our results reveal

Immunoblot studies of synaptic membranes isolated from rat brain using antibodies raised against a previously purified glutamate-binding protein (GBP) indicated labeling of an approx. 70-kDa protein band. Since the antibodies used were raised against a 14-kDa GBP, the present studies were undertaken to explore the possibility that the 14-kDa protein may have been a proteolytic fragment of a larger M/sub r/ protein in synaptic membranes. The major protein enriched in the most highly purified fractions was a 71-kDa glycoprotein, but a 63-kDa protein was co-purified during most steps of the isolation procedure. The glutamate-binding characteristics of these isolated protein fractions were very similar to those previously described for the 14-kDa GBP, including estimated dissociation constants for L-glutamate binding of 0.25 and 1 /sup +/M, inhibition of glutamate binding by azide and cyanide, and a selectivity of the ligand binding site for L-glutamate and L-aspartate. The neuroexcitatory analogs of L-glutamate and L-aspartate, ibotenate, quisqualate, and D-glutamate, inhibited L(/sup 3/H)glutamate binding to the isolated proteins, as did the antagonist of L-glutamate-induced neuronal excitation, L-glutamate diethylester. On the basis of the lack of any detectable glutamate-related enzyme activity associated with the isolated proteins and the presence of distinguishing sensitivities to analogs that inhibit glutamate transport carriers in synaptic membranes, it is proposed that the 71-kDa protein may be a component of a physiologic glutamate receptor complex in neuronal membranes.

Hormonal, physiological, and biochemical changes occurring in dehydrated patients could alter the pharmacokinetics of the drugs; therefore, the pharmacokinetics of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous administration of the drug at 50 mg/kg to control and 72-hr water-deprived rats. The impaired kidney and liver functions were observed in water-deprived rats on the basis of tissue microscopic examination. After intravenous infusion of the drug to water-deprived rats, the plasma concentrations of DA-1131 were higher and this resulted in a significantly greater total area under the plasma concentration-time curve from time zero to time infinity than those in control rats (4520 versus 3760 microg min/ml). This could be due to significantly slower total body clearance (CL) of DA-1131 in water-deprived rats (9.81 versus 14.1 ml/min/kg). The significantly slower CL of DA-1131 in water-deprived rats was due to significant decrease in both renal clearance (2.87 versus 5.13 ml/min/kg because of a significant decrease in 8-hr urinary excretion of unchanged DA-1131 [28.4 versus 39.9% of the intravenous dose] due to impaired kidney function) and nonrenal clearance (6.82 versus 8.66 ml/min/kg because of a significant decrease in the metabolism of DA-1131 in the kidney, as proved by the significant decrease in total renal DHP-I enzyme activity [1900 versus 2130 mU/each kidney]) in water-deprived rats. Water-deprivation did not alter the affinity of rat tissues to DA-1131.

The aim of this survey was to gather data from both implant recipients and professionals on the ease of use of the Naída CI Q70 (Naída CI) sound processor from Advanced Bionics and on the usefulness of the new functions and features available. A secondary objective was to investigate fitting practices with the new processor. A comprehensive user satisfaction survey was conducted in a total of 186 subjects from 24 centres. In parallel, 23 professional questionnaires were collected from 11 centres. Overall, there was high satisfaction with the Naída CI processor from adults, children, experienced and new CI users as well as from professionals. The Naída CI processor was shown as being easy to use by all ages of recipients and by professionals. The majority of experienced CI users rated the Naída CI processor as being similar or better than their previous processor in all areas surveyed. The Naída CI was recommended by the professionals for fitting in all populations. Features like UltraZoom, ZoomControl and DuoPhone would not be fitted to very young children in contrast to adults. Positive ratings were obtained for ease of use, comfort and usefulness of the new functions and features of the Naída CI sound processor. Seventy-seven percent of the experienced CI users rated the new processor as being better than their previous sound processor from a general point of view. The survey also showed that fitting practices were influenced by the age of the user.

Objective(s) Garlic (Allium sativum) is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, and anticoagulant. One of the major purified garlic protein components is the 47 kDa protein. In this study, the effect of 47 kDa protein extracted from aged garlic (AGE) was evalua Materials and Methods Forty seven kDa protein was purified from AGE by ammonium sulfate precipitation and gel filtration. SDS-PAGE was used to determine the molecular weight and purity of the isolated protein. DCs were purified from spleen of BALB/c mice by Nycodenz centrifugation and their adhesiveness to the plastic dish. The 47 kDa protein isolated from AGE was added to DCs medium during the overnight culture and the expression of DC surface markers was assessed via flowcytometry. Results The 47 kDa protein-treated DCs lowered the expression of DC maturation markers including: CD40, CD86 and MHC-II in comparison with non-treated DCs; (median of 41% versus 47%, 84% versus 91% and 83% versus 90%, respectively) but we observed no statistical difference between the two groups. Conclusion Upon treatment with DCs with 47 kDa protein, DCs down regulated the expression of costimulatory and MHC-II surface molecules, which is similar to tolerogenic DC phenotype. According to the results of the present study, we found that 47 kDa protein purified from AGE can be considered as a potential candidate to generate tolerogenic DCs in vitro. PMID:23493446

The aim of this survey was to gather data from both implant recipients and professionals on the ease of use of the Naída CI Q70 (Naída CI) sound processor from Advanced Bionics and on the usefulness of the new functions and features available. A secondary objective was to investigate fitting practices with the new processor. A comprehensive user satisfaction survey was conducted in a total of 186 subjects from 24 centres. In parallel, 23 professional questionnaires were collected from 11 centres. Overall, there was high satisfaction with the Naída CI processor from adults, children, experienced and new CI users as well as from professionals. The Naída CI processor was shown as being easy to use by all ages of recipients and by professionals. The majority of experienced CI users rated the Naída CI processor as being similar or better than their previous processor in all areas surveyed. The Naída CI was recommended by the professionals for fitting in all populations. Features like UltraZoom, ZoomControl and DuoPhone would not be fitted to very young children in contrast to adults. Positive ratings were obtained for ease of use, comfort and usefulness of the new functions and features of the Naída CI sound processor. Seventy-seven percent of the experienced CI users rated the new processor as being better than their previous sound processor from a general point of view. The survey also showed that fitting practices were influenced by the age of the user. PMID:28217275

Research is needed to improve efficiency of phytoextraction of heavy metals from contaminated soils. A pot experiment was carried out to study the effects of plant growth regulators (PGRs) (diethyl aminoethyl hexanoate (C18H33NO8, DA-6) and gibberellic acid 3 (C19H22O6, GA3)) and/or EDTA on Cd extraction, subcellular distribution and chemical forms in Lolium perenne. The addition of EDTA or PGRs significantly enhanced Cd extraction efficiency (P<0.05), with the decreasing order of: 1 μM DA-6>10 μM DA-6>10 μM GA3>2.5 mmol kg(-1) EDTA>other treatments of PGR alone. PGRs+EDTA resulted in a further increase in Cd extraction efficiency, with EDTA+1 μM DA-6 being the most efficient. At the subcellular level, about 44-57% of Cd was soluble fraction, 18-44% in cell walls, and 12-25% in cellular organelles fraction. Chemical speciation analysis showed that 40-54% of Cd was NaCl extractable, 7-23% HAc extractable, followed by other fractions. EDTA increased the proportions of Cd in soluble and cellular organelles fraction, as well as the metal migration in shoot; therefore, the toxicity to plant increased and plant growth was inhibited. Conversely, PGRs fixed more Cd in cell walls and reduced Cd migration in shoot; thus, metal toxicity was reduced. In addition, PGRs promoted plant biomass growth significantly (P<0.05), with 1 μM DA-6 being the most effective. A combination of DA-6/GA3 with EDTA can alleviate the adverse effect of EDTA on plant growth, and the treatment of EDTA+1 μM DA-6 appears to be optimal for improving the remediation efficiency of L. perenne for Cd contaminated soil.

We have explored a role for the adenovirus (Ad5) E1b58kDa/p53 protein complex in adenovirus replication. This was done by using virus mutants containing different defects in the E1b58kDa gene and cell lines that express either a wild-type p53 protein or a mutant p53 protein. We find that infection of wild-type p53-containing cells with wild-type Ad5 causes a shutoff of p53 and alpha-actin protein synthesis by distinct mechanisms, but neither occurs in mutant p53 cells. Our data also indicate that the shutoff is dependent on formation of the p53/E1b complex and may also involve another virus protein, E4ORF6. Following from these observations we asked whether failure to form the complex resulted in impaired adenovirus replication. Our experiments showed that neither wild-type Ad5 nor the E1b mutant dl338 could replicate in cells expressing a mutant p53 protein, but that wild-type adenovirus replicated well in wild-type p53-expressing cells. Collectively, our data suggest that the interaction between p53 and the E1b58kDa protein is necessary for efficient adenovirus replication. This is the first time such a direct link between the complex and virus replication has been demonstrated. These data raise serious questions about the usefulness of E1b-defective viruses in tumor therapy.

This study aimed to observe the effects of Se deficiency on epiphyseal plates of two generation DA rats fed with artificial total synthetic low Se diet. All F0 and F1 DA rats were fed with synthetic low Se diet (SeD group) and low Se diet supplied with Se (SeS group). The levels of selenium and enzyme activities of GPx were detected in plasma of the rats. General growth of bone and articular cartilage was measured macroscopically and microscopically. The epiphyseal plate of femur heads or tibia were obtained to histological and immunohistochemical examinations. The cartilage from left knee joints and femur heads was used to detect the gene expression of collagens, ADAMTSs and several selenoproteins by RT-qPCR. Two generation SeD rats showed Se insufficiency status. The thicknesses of the femur and tibial epiphyseal plates in both F0 and F1 SeD rats were significantly less than that of SeS rats. In F1 generation, SeD rats showed much fewer proliferative chondrocyte layers than SeS ones. Importantly, two generation SeD rats both showed significantly more serious pathological changes of epiphyseal plates. In two generation rats, gene expressions of COL II, GPx1 and GPx4 were significantly down-regulated in SeD rats than SeS ones; meanwhile ADAMTS-4 showed an up-regulated expression in cartilage. Dietary Se deficiency can apparently cause epiphyseal plate lesion and decrease cartilage type II collagen production and GPx1 activity in two generation DA rats fed with the artificial total synthesis low Se diet.

The latest generation Da Vinci(®) Xi™ Surgical System Robot released has not been evaluated to date in transoral surgery for head and neck cancers. We report here the 1-year results of a non-randomized phase II multicentric prospective trial aimed at assessing its feasibility and technical specificities. Our primary objective was to evaluate the feasibility of transoral robotic surgery using the da Vinci(®) Xi™ Surgical System Robot. The secondary objective was to assess peroperative outcomes. Twenty-seven patients, mean age 62.7 years, were included between May 2015 and June 2016 with tumors affecting the following sites: oropharynx (n = 21), larynx (n = 4), hypopharynx (n = 1), parapharyngeal space (n = 1). Eighteen patients were included for primary treatment, three for a local recurrence, and six for cancer in a previously irradiated field. Three were reconstructed with a FAMM flap and 6 with a free ALT flap. The mean docking time was 12 min. "Chopsticking" of surgical instruments was very rare. During hospitalization following surgery, 3 patients experienced significant bleeding between day 8 and 9 that required surgical transoral hemostasis (n = 1) or endovascular embolization (n = 2). Transoral robotic surgery using the da Vinci(®) Xi™ Surgical System Robot proved feasible with technological improvements compared to previous generation surgical system robots and with a similar postoperative course. Further technological progress is expected to be of significant benefit to the patients.

The aim of the study was to find out and to analyse the text by Vitruvius which inspired the famous drawing by Leonardo da Vinci (circa 1490) kept in the Galleria dell'Accademia, in Venezia, Italy: the man inscribed in one circle and in one square. The book "de Architectura" by Vitruvius Marcus Pollio was printed several times since the Renaissance when both the roman architecture of antiquity and this text became very popular. From a French translation by Claude Perrault in 1864, it became easy to find a French translation with the original text in Latin (Paris, 2003, Les Belles Lettres, French text by Pierre Gros). The drawing by Leonardo da Vinci illustrates with great accuracy and fidelity the quotation of Vitruvius (with the exception of two of the 12 main relationships). The genius of Leonardo da Vinci was to keep only one trunk, head and neck for two pairs of limbs: scapular and pelvic; to make the circle tangent to the lower edge of the square; to adjust a few features of the quotation for the equilibrium of the whole figure; and of course to bring his incredible skill as a drawer (one of the best of his century). The drawing was made on a sheet of paper 344x245mm, in black ink which became dark brown with time; several lines complete the figure above and below; a short caption and a horizontal scale appear just under the drawing. The celebrity of the drawing, a symbol of the Renaissance, of the equilibrium of man and mankind, of the universality of the artists and intellectuals of the time (Humanism) made it iconic and it has been constantly reproduced and adapted especially for advertisement and logos, not only in the medical field.

Many advanced models in physics use a simpler system as the foundation upon which problemspecific perturbation terms are added. There are many mathematical methods in perturbation theory which attempt to solve or at least approximate the solution for the advanced model based on the solution of the unperturbed system. The analytical approaches have the advantage that their approximation is an algebraic expression relating all involved quantities in the calculated solution up to a certain order. However, the complexity of the calculation often increases drastically with the number of iterations, variables, and parameters considered. On the other hand, the computer-based numerical approaches are fast once implemented, but their results are only numerical approximations without a symbolic form. A numerical integrator, for example, takes the initial values and integrates the ordinary differential equation up to the requested final state and yields the result as specific numbers. Therefore, no algebraic expression, much less a parameter dependence within the solution is given. The method presented in this work is based on the differential algebra (DA) framework, which was first developed to its current extent by Martin Berz et. al [3, 4, 5]. The used DA Normal Form Algorithm is an advancement by Martin Berz from the first arbitrary order algorithm by Forest, Berz, and Irwin [13], which was based on an DA-Lie approach. Both structures are already implemented in COSY INFINITY [18] documented in [7, 16, 17]. The result of the presented method is a numerically calculated algebraic expression of the solution up to an arbitrary truncation order. This method combines the effectiveness and automatic calculation of a computer-based numerical approximation and the algebraic relation between the involved quantities.

A plastidic 112-kDa starch phosphorylase (SP) has been identified in the amyloplast stromal fraction of maize. This starch phosphorylase was purified 310-fold from maize endosperm and characterized with respect to its enzymological and kinetic properties. The purification procedure included ammonium sulfate fractionation, Sephacryl 300 HR chromatography, affinity starch adsorption, Q-Sepharose, and Mono Q chromatography. The procedure resulted in a nearly homogeneous enzyme preparation as determined by native and SDS-polyacrylamide gel electrophoresis. Anti-SP antibodies recognized the purified 112-kDa SP enzyme and N-terminal amino acid sequence analysis confirmed that the purified enzyme is the amyloplast stromal 112-kDa SP. Analysis of the purified enzyme by Superose 6 gel filtration chromatography indicated that the native enzyme consisted of two identical subunits. The pH optimum for the enzyme was 6.0 in the synthetic direction and 5.5 in the phosphorolytic direction. SP activity was inhibited by thioreactive agents, diethyl pyrocarbonate, phenylglyoxal, and ADP-glucose. The activation energies for the synthetic and phosphorolytic reactions were 11.1 and 16.9 kcal/mol, respectively, and the enzyme was thermally labile above 50 degrees C. Results of kinetic experiments indicated that the enzyme catalyzes its reaction via a sequential Bi Bi mechanism. The Km value for amylopectin was eight-fold lower than that of glycogen. A kinetic analysis indicated that the phosphorolytic reaction was favored over the synthetic reaction when malto-oligosaccharides (4 to 7 units) were used as substrates. The specificity constants (Vmax/Km) of the enzyme measured in either the synthetic or the phosphorolytic directions increased with increasing chain length.

Ultraviolet spectroscopic observations of two relatively cool DA white dwarfs, L481 - 60 (= WD 1544 - 37) and BPM 1266 ( = WD 2105 - 82), with the International Ultraviolet Explorer (IUE) satellite show a strong drop in their spectral energy distributions below 1600 A. Published model atmospheres and thier visual spectra suggest that these two stars have effective temperatures in the vicinity of 9,000-10,000 K, and it is proposed that the 1600 A feature could be due to the 342(1S) 3s2(1S) photoionization edge of Mg I.

The works of physician and naturalist Emílio Joaquim da Silva Maia (1808-59) can be viewed as a scientific project that discovers Brazil and its inhabitants. Maia's nationalism and his romantic view of nature formed the underpinnings of his scientific theories, especially his studies on zoological geography. He subordinated the issue of the biological specificity of different regions of the world to his era's debates on the construction of Brazil as an independent nation. In his interpretations of European natural history, Maia endeavored to understand Brazilian nature as a specific achievement of the Cosmos, in keeping with Alexander von Humboldt's approach.

A customized quadrupole ion-trap mass spectrometer (QITMS) has been built to satisfy a need for a compact, rugged instrument for measuring small concentrations of hydrogen, helium, oxygen, and argon in a nitrogen atmosphere. This QITMS can also be used to perform quantitative analyses of other gases within its molecular-mass range, which is 2 to 50 daltons (Da). (More precisely, it can be used to perform quantitative analysis of gases that, when ionized, are characterized by m/Z ratios between 2 and 50, where m is the mass of an ion in daltons and Z is the number of fundamental electric charges on the ion.

This paper offers a commentary on three aspects of the Supreme Court's recent decision (2011Da22092). First, contrary to the Court's finding, this paper argues that epidemiological evidence can be used to estimate the probability that a given risk factor caused a disease in an individual plaintiff. Second, the distinction between specific and non-specific diseases, upon which the Court relies, is shown to be without scientific basis. Third, this commentary points out that the Court's finding concerning defect of expression effectively enables tobacco companies to profit from the efforts of epidemiologists and others involved in public health to raise awareness of the dangers of smoking.

Ongoing excavations in the Middle Paleolithic levels at the Gruta da Oliveira, Portugal have yielded four fragmentary human remains, a manual phalanx and an ulna from levels 9 and 10, and a humerus and a tibia from levels 18 and 19. The first two remains date to approximately 39 ka 14C BP ( approximately 43.5 ka cal BP), whereas the latter two derive from earlier in oxygen isotope stage 3. The preserved portions of the phalanx, humerus, and tibia align them morphologically with the Neandertals. In addition, the Oliveira 4 tibial diaphysis shows evidence of carnivore (probably canid) gnawing.

I(It? This?) presents the general characteristics of the Revista Brasileira de História da Medicina, which contributed for the emergence of the field of medicine history in Brazil by inciting bibliographic production on the subject. The purpose of our analysis is to foster research on the history of medicine and of the sciences. From the description of the editorial aspects of the journal one can have an idea of how the research field was organized between 1940 and 1960. The periodical also allows for an overview of the exchange occurring between Brazilian and foreign historian physicians at that time.

Tristan da Cunha Island is one of the classical hot spots in the Atlantic Ocean, situated at the western end of the aseismic Walvis Ridge which forms a connection to the Cretaceous Etendeka flood basalt province in northwestern Namibia. The discussion about its source (in shallow asthenosphere or deeper mantle) have not reached consensus yet because of lack of the geophysical observations in the area. A marine magnetotelluric (MT) experiment was conducted together with seismological observations in the area in 2012-2013 through a German-Japanese collaboration with the goal to constrain the physical state of the mantle beneath the area. A total of 26 MT seafloor stations were deployed around the Tristan da Cunha Islands and available data were retrieved and processed from 24 stations. We applied iterative topographic effect correction and one-dimensional (1-D) conductivity structure inversion to the data. Then, three-dimensional (3-D) inversion analysis incorporating the topographic effect was carried out, using the 1-D model as the initial model. The local small-scale topography and the far continental coast effects are incorporated as the distortion term in the 3-D inversion. The preliminary result of our analysis shows no evidence of a significant conductive anomaly arising from the mantle transition zone, suggesting that the current magmatic source (major place of melting) of the hotspot activity is in the shallow upper mantle. This is in contrast to results from geochemical analysis, in which samples along the Tristan track exhibit an ocean-island-basalt-type incompatible element pattern pointing to a deep mantle source of the melt. Our findings therefore might indicate that the deep mantle up-welling underneath Tristan da Cunha Islands may be almost dead. A conductive anomaly at approx. 100 km depth in our derived conductivity model to the southwest of Tristan da Cunha Islands suggests an interaction between the mid-ocean ridge and/or up-welling further south

Genome-wide profiling of transcription factors based on massive parallel sequencing of immunoprecipitated chromatin (ChIP-seq) requires nanogram amounts of DNA. Here we describe a high-fidelity, single-tube linear DNA amplification method (LinDA) for ChIP-seq and reChIP-seq with picogram DNA amounts obtained from a few thousand cells. This amplification technology will facilitate global analyses of transcription-factor binding and chromatin with very small cell populations, such as stem or cancer-initiating cells.

Madonna dei Fusi (`Madonna of the Yarnwider') is a spectacular example of Italian Renaissance painting, attributed to Leonardo da Vinci. The aim of this study is to give an account of past restoration procedures. The evidence of a former retouching campaign will be presented with cross-sectional images obtained non-invasively with Optical Coherence Tomography (OCT). Specifically, the locations of overpaintings/retouchings with respect to the original paint layer and secondary varnishes will be given. Additionally, the evidence of a former transfer of the pictorial layer to the new canvas support by detecting the presence of its structure incised into paint layer will be shown.

The article focuses on a rare example of a miniature skull of unknown origin. The profoundness of the anatomical details, conjoint with outstanding virtuosity, reminds of Leonardo da Vinci's anatomical skull studies and asks for additional interpretation beside the emblematic "memento mori"-character. Following the miscellaneous topics of his skull studies an anatomical-anthropological interpretation is proposed. For such a project the mergence of anthropology, history of medicine and history of art was mandatory. Concerning some discrepancies within the anatomical realism, the depiction of a pathology is discussed and beyond the visualisation of a historic concept of brain function.

Multicolor images of the new optical transient in NGC 300, discovered by B. Monard (CBET #2289 and private communication), were obtained on 2010 May 25.37 by J. Espinoza with the SMARTS 1.3m telescope at Cerro Tololo and the ANDICAM camera. The transient has received the designation SN 2010da, although spectroscopic observations and the low luminosity suggest that it is most probably an LBV-like outburst on a dust-enshrouded massive star and not a true supernova (e.g., ATEL #2632, #2633, #2636, #2637, #2638).

DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation.

Background The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation

We present multi-epoch mid-infrared (IR) photometry and the optical discovery observations of the “impostor” supernova (SN) 2010da in NGC 300 using new and archival Spitzer Space Telescope images and ground-based observatories. The mid-infrared counterpart of SN 2010da was detected as Spitzer Infrared Intensive Transient Survey (SPIRITS) 14bme in the SPIRITS, an ongoing systematic search for IR transients. Before erupting on 2010 May 24, the SN 2010da progenitor exhibited a constant mid-IR flux at 3.6 and only a slight ˜10% decrease at 4.5 μm between 2003 November and 2007 December. A sharp increase in the 3.6 μm flux followed by a rapid decrease measured ˜150 days before and ˜80 days after the initial outburst, respectively, reveal a mid-IR counterpart to the coincident optical and high luminosity X-ray outbursts. At late times, after the outburst (˜2000 days), the 3.6 and 4.5 μm emission increased to over a factor of two times the progenitor flux and is currently observed (as of 2016 Feb) to be fading, but still above the progenitor flux. We attribute the re-brightening mid-IR emission to continued dust production and increasing luminosity of the surviving system associated with SN 2010da. We analyze the evolution of the dust temperature (T d ˜ 700-1000 K), mass (M d ˜ 0.5-3.8 × 10-7 M ⊙), luminosity (L IR ˜ 1.3-3.5 × 104 L ⊙), and the equilibrium temperature radius (R eq ˜ 6.4-12.2 au) in order to resolve the nature of SN 2010da. We address the leading interpretation of SN 2010da as an eruption from a luminous blue variable high-mass X-ray binary (HMXB) system. We propose that SN 2010da is instead a supergiant (sg)B[e]-HMXB based on similar luminosities and dust masses exhibited by two other known sgB[e]-HMXB systems. Additionally, the SN 2010da progenitor occupies a similar region on a mid-IR color-magnitude diagram (CMD) with known sgB[e] stars in the Large Magellanic Cloud. The lower limit estimated for the orbital eccentricity of the sg

The hepatoprotective effect of DA-9601, a quality-controlled extract of Artemisia asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCl4) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of DA-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or CCl4 (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of DA-9601 reduced the elevation of serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. DA-9601 also prevented APAP- and CCl4-induced hepatic glutathione (GSH) depletion and CCl4-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a dose-dependent manner. These findings suggest that pretreatment with DA-9601 may reduce chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.

AIM: To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat’s stomach to naproxen (NAP). METHODS: Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). RESULTS: Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. CONCLUSION: These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved. PMID:16437715

Vŗkşăyurvĕda of Parăśara is a great contribution to the Botany in ancient India. N.N. Sircar and Roma sarkar edited this text with English translation. Notes with comparative references of modern botany were added. This book can be placed in all probability in between 1st century B.C to 4th century A.D by its linguistic style. Many scientific branches of Botany including origin of life, ecology, distribution of forests, morphology, classification, nomenclature, histology and physiology were dealt in this ancient work. Though it is presumed that this book was written by Parăśara to teach Botany to preparatory to Ayurvĕda studies to ancient Ayurvĕda students, it is true to the Ayurvĕda personals and other disciplines related to Botany of present day as well. Aim of this article is to attract the attention of all scholars who are related to Ayurvĕda and Botany and to feel the depth of the knowledge of ancient Indian botany.

The maize opaque2 (o2) mutant has a high nutritional value but it develops a chalky endosperm that limits its practical use. Genetic selection for o2 modifiers can convert the normally chalky endosperm of the mutant into a hard, vitreous phenotype, yielding what is known as quality protein maize (QPM). Previous studies have shown that enhanced expression of 27-kDa γ-zein in QPM is essential for endosperm modification. Taking advantage of genome-wide association study analysis of a natural population, linkage mapping analysis of a recombinant inbred line population, and map-based cloning, we identified a quantitative trait locus (qγ27) affecting expression of 27-kDa γ-zein. qγ27 was mapped to the same region as the major o2 modifier (o2 modifier1) on chromosome 7 near the 27-kDa γ-zein locus. qγ27 resulted from a 15.26-kb duplication at the 27-kDa γ-zein locus, which increases the level of gene expression. This duplication occurred before maize domestication; however, the gene structure of qγ27 appears to be unstable and the DNA rearrangement frequently occurs at this locus. Because enhanced expression of 27-kDa γ-zein is critical for endosperm modification in QPM, qγ27 is expected to be under artificial selection. This discovery provides a useful molecular marker that can be used to accelerate QPM breeding.

Agarose and polyacrylamide gel electrophoresis systems for the molecular mass-dependent separation of hyaluronan (HA) in the size range of approximately 5-500 kDa were investigated. For agarose-based systems, the suitability of different agarose types, agarose concentrations, and buffer systems was determined. Using chemoenzymatically synthesized HA standards of low polydispersity, the molecular mass range was determined for each gel composition over which the relationship between HA mobility and logarithm of the molecular mass was linear. Excellent linear calibration was obtained for HA molecular mass as low as approximately 9 kDa in agarose gels. For higher resolution separation, and for extension to molecular masses as low as approximately 5 kDa, gradient polyacrylamide gels were superior. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in a sample as well as calculation of weight-average and number-average values. The methods were validated for polydisperse HA samples with viscosity-average molecular masses of 112, 59, 37, and 22 kDa at sample loads of 0.5 μg (for polyacrylamide) to 2.5 μg (for agarose). Use of the methods for electrophoretic mobility shift assays was demonstrated for binding of the HA-binding region of aggrecan (recombinant human aggrecan G1-IGD-G2 domains) to a 150-kDa HA standard.

Although the control of organ size is a fundamental question in developmental biology, little is known about the genetic and molecular mechanisms that determine the final size of seeds in plants. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligases DA2 and ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to restrict seed growth in Arabidopsis thaliana. Here, we describe UBIQUITIN-SPECIFIC PROTEASE15 (UBP15), encoded by SUPPRESSOR2 OF DA1 (SOD2), which acts maternally to regulate seed size by promoting cell proliferation in the integuments of ovules and developing seeds. The sod2/ubp15 mutants form small seeds, while overexpression of UBP15 increases seed size of wild-type plants. Genetic analyses indicate that UBP15 functions antagonistically in a common pathway with DA1 to influence seed size, but does so independently of DA2 and EOD1. Further results reveal that DA1 physically associates with UBP15 in vitro and in vivo and modulates the stability of UBP15. Therefore, our findings establish a genetic and molecular framework for the regulation of seed size by four ubiquitin-related proteins DA1, DA2, EOD1, and UBP15 and suggest that they are promising targets for increasing seed size in crops. PMID:24585836

Human interaction environments (HIE) must be understood as any place where people carry out their daily life, including their work, family life, leisure and social life, interacting with technology to enhance or facilitate the experience. The integration of technology in these environments has been achieved in a disorderly and incompatible way, with devices operating in isolated islands with artificial edges delimited by the manufacturers. In this paper we are presenting the UniDA framework, an integral solution for the development of systems that require the integration and interoperation of devices and technologies in HIEs. It provides developers and installers with a uniform conceptual framework capable of modelling an HIE, together with a set of libraries, tools and devices to build distributed instrumentation networks with support for transparent integration of other technologies. A series of use case examples and a comparison to many of the existing technologies in the field has been included in order to show the benefits of using UniDA. PMID:22163700

For several years the PanDA Workload Management System has been the basis for distributed production and analysis for the ATLAS experiment at the LHC. Since the start of data taking PanDA usage has ramped up steadily, typically exceeding 500k completed jobs/day by June 2011. The associated monitoring data volume has been rising as well, to levels that present a new set of challenges in the areas of database scalability and monitoring system performance and efficiency. These challenges are being met with an R&D effort aimed at implementing a scalable and efficient monitoring data storage based on a noSQL solution (Cassandra). We present our motivations for using this technology, as well as data design and the techniques used for efficient indexing of the data. We also discuss the hardware requirements as they were determined by testing with actual data and realistic rate of queries. In conclusion, we present our experience with operating a Cassandra cluster over an extended period of time and with data load adequate for planned application.

A wide range of recombinant proteins from Eimeria species have been reported to offer some degree of protection against infection and disease, but the specific biological function of these proteins is largely unknown. Previous studies have demonstrated a 19-kDa protein of unknown function designated SZ-1 in sporozoites and merozoites of Eimeria acervulina that can be used to confer partial protection against coccidiosis. Reverse transcriptase-polymerase chain reaction indicated that the gene for SZ-1 is expressed by all the asexual stages of Eimeria tenella. Rabbit antisera to recombinant SZ-1 recognized an approximately 19-kDa protein from extracts of E. tenella sporozoites, merozoites, sporulated oocysts, and oocysts in various stages of sporulation. Immunofluorescence antibody staining indicated specific staining of E. tenella sporozoites and merozoites. Staining was most intense in the cytoplasm of the posterior end of the parasite. The primary amino acid sequence of the gene for E. tenella SZ-1 deduced from the E. tenella genome indicated a conserved domain for the actin-regulatory protein profilin. A conserved binding site for poly-L-proline (PLP), characteristic of profilin was also observed. SZ-1 was separated from soluble extract of E. tenella proteins by affinity chromatography using a PLP ligand, confirming the ability of SZ-1 to bind PLP. SZ-1 also partially inhibited the polymerization of actin. The current results are consistent with the classification of SZ-1 as a profilin-related protein.

Tuberculosis diagnosis bases on clinical and radiological symptoms and identification of mycobacteria. Accuracy of both methods is limited. Therefore reliable serological test would have considerable advantage. The present study was aimed at evaluating IgG-mediated immune response against specific mycobacterial antigens 38 kDa in group of 200 patients and control subjects. Our material consisted of 104 tuberculosis patients, 25 with sarcoidosis, 24 with lung cancer, 13 with bacterial or fungal pulmonary infection, 8 with mycobacterial infections other than tuberculosis and 26 healthy persons. We used commercially available ELISA based kits (Pathozyme TB-complex). Specificity of 100% and sensitivity of 49% was achieved. Sensitivity increased to 59% in chronic cases and to 52% in culture positive cases. Sensitivity decreased to only 14% in group of new culture negative cases. Measurement of IgG serum level against 38 kDa can be helpful in tuberculosis diagnosis. As the test lacks falsely positive results it indicates its high positive predictive value.

Blood species identification is of great significance for blood supervision and wildlife investigations. The current methods used to identify the blood species are destructive. Near-Infrared spectroscopy method is known for its non-invasive properties. In this research, we combined Near-Infrared diffuse transmitted spectra and Partial Least Square Discrimination Analysis (PLS-DA) to identify three blood species, including macaque, human and mouse. Blind test and external test were used to assess the PLS-DA model. The model performed 100% accuracy in its identification between three blood species. This approach does not require a specific knowledge of biochemical features for each individual class but relies on a spectroscopic statistical differentiation of the whole components. This is the first time to demonstrate Near-Infrared diffuse transmitted spectra have the ability to identify the species of origin of blood samples. The results also support a good potential of absorption and scattering spectroscopy for species identification in practical applications for real-time detection.

Cleavage factor Im is an essential component of the pre-messenger RNA 3'-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor Im is an oligomer composed of a small 25 kDa subunit (CF Im25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein-protein interactions are thought to be facilitated by the Nudix domain of CF Im25, a hydrolase motif with a characteristic {alpha}/{beta}/{alpha} fold and a conserved catalytic sequence or Nudix box. We present here the crystal structures of human CF Im25 in its free and diadenosine tetraphosphate (Ap4A) bound forms at 1.85 and 1.80 Angstroms, respectively. CF Im25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF Im25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap4A. The complex and apo protein structures provide insight into the active oligomeric state of CF Im and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3'-end processing.

The Duchenne muscular dystrophy gene gives rise to transcripts of several lengths. These mRNAs differ in their coding content and tissue distribution. The 14 kb mRNA encodes dystrophin, a 427 kDa protein found in muscle and brain, and the short transcripts described encode DP71, a 77 kDa protein found in various organs. These short transcripts have many features common to the deduced primary structure of dystrophin, especially in the cysteine-rich specific C-terminal domains. The dystrophin C-terminal domain could be involved in membrane anchorage via the glycoprotein complex, but such a functional role for these short transcript products has yet to be demonstrated. Here we report the first isolation of a short transcript product from saponin-solubilized cardiac muscle membranes using alkaline buffer and affinity chromatography procedures. This molecule was found to be glycosylated and could be easily dissociated from cardiac muscle and other non-muscle tissues such as brain and liver. DP71-specific monoclonal antibody helped to identify this molecule as being related to the dystrophin gene family. Immunofluorescence analysis of bovine or chicken cardiac muscle showed a periodic distribution of DP71 in transverse T tubules and this protein was co-localized with the dystrophin glycoprotein complex in the Z-disk area.

A portrait of uncertain origin recently came to light which, after extensive research and examination, was shown to be that rarest of things: a newly discovered Leonardo da Vinci painting entitled La Bella Principessa. This research presents a new illusion which is similar to that identified in the Mona Lisa; La Bella Principessa's mouth appears to change slant depending on both the Viewing Distance and the Level of Blur applied to a digital version of the portrait. Through a series of psychophysics experiments, it was found that a perceived change in the slant of the La Bella Principessa's mouth influences her expression of contentment thus generating an illusion that we have coined the "uncatchable smile". The elusive quality of the Mona Lisa's smile has been previously reported (Science, 290 (2000) 1299) and so the existence of a similar illusion in a portrait painted prior to the Mona Lisa becomes more interesting. The question remains whether Leonardo da Vinci intended this illusion. In any case, it can be argued that the ambiguity created adds to the portrait's allure.

Leonardo Da Vinci and Andreas Vesalius were two important renaissance persons; Vesalius was a surgeon-anatomist who delivered innovative work on the study of the human body, Leonardo da Vinci was an artist who delivered strikingly accurate and beautiful drawings on the human body. Below we compare both masters with regard to their knowledge of the working of the muscles, their method and system of dissection and their system and presentation of the drawings. The investigation consisted of a comparison between both anatomists, in particular concerning their study on the shoulder girdle and spine, by reviewing their original work as well as already existing literature on this subject. The investigation led to the conclusion that the drawings mentioned meant a change in history, and were of high quality, centuries ahead of their time. Both were anatomists, both were revolutionary, only one changed history at the moment itself, while the other changed history centuries later. Leonardo has made beautiful drawings that are at a match with the drawings of today or are even better. Vesalius set the start for medicine as a science as it is until this day. Their lives differed as strongly as their impact. In the light of their time, the achievement they made was extraordinary.

We report the detection, in archival ROSAT and ASCA observations, of X-ray emission from the direction of DA 495 (G65.7+1.2), a likely supernova remnant of uncertain classification but with similarities to the Crab Nebula. An unusual feature of the radio nebula is its annular morphology, with a flux minimum at the geometrical center. In the soft X-ray band, the ROSAT data resolve a compact source near the edge of the central radio hole ; the hard X-ray morphology, at the limit of ASCA's spatial resolution, is suggestive of extended plerionic emission dropping off from a central flux maximum coincident with the ROSAT source. The spectrum is well-described by a power-law with photon index approximately 1.7, and the X-ray flux is roughly constant with time. Taken together, this evidence suggests identification of the X-ray source with a magnetospherically active neutron star and its associated wind nebula. Timing analysis of the ASCA data yields only a weak upper bound on pulsations with periods longer than approximately 30 ms. These results reveal for the first time the high-energy engine that powers the synchrotron nebula, and strengthen the classification of DA 495 as a plerionic supernova remnant, one that may represent a late evolutionary stage of Crab-like nebulae.

Polymer solar cells (PSCs) consisting of fullerene bis-adduct and poly(3-hexylthiophene) (P3HT) blends have shown higher efficiencies than P3HT:phenyl C(61)-butyric acid methyl ester (PCBM) devices, because of the high-lying lowest unoccupied molecular orbital (LUMO) level of the fullerene bis-adducts. In contrast, the use of fullerene bis-adducts in donor-acceptor (DA) copolymer systems typically causes a decrease in the device's performance due to the decreased short-circuit current (J(SC)) and the fill factor (FF). However, the reason for such poor performance in DA copolymer:fullerene bis-adduct blends is not fully understood. In this work, bulk-heterojunction (BHJ)-type PSCs composed of three different electron donors with four different electron acceptors were chosen and compared. The three electron donors were (1) poly[(4,8-bis-(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene)-2,6-diyl-alt-(5-octylthieno[3,4-c]pyrrole-4,6-dione)-1,3-diyl] (PBDTTPD), (2) poly[(4,8-bis-(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene)-2,6-diyl-alt-(4-(2-ethylhexanoyl)-thieno[3,4-b]thiophene)-2,6-diyl] (PBDTTT-C), and (3) P3HT polymers. The four electron acceptors were (1) PCBM, (2) indene-C(60) monoadduct (ICMA), (3) indene-C(60) bis-adduct (ICBA), and (4) indene-C(60) tris-adduct (ICTA). To understand the difference in the performance of BHJ-type PSCs for the three different polymers in terms of the choice of fullerene acceptor, the structural, optical, and electrical properties of the blends were measured by the external quantum efficiency (EQE), photoluminescence, grazing incidence X-ray scattering, and transient absorption spectroscopy. We observed that while the molecular packing and optical properties cannot be the main reasons for the dramatic decrease in the PCE of the DA copolymers and ICBA, the value of the driving force for charge transfer (ΔG(CT)) is a key parameter for determining the change in J(SC) and device efficiency in the DA copolymer- and P3HT-based PSCs in

Three n-type alternating D-A copolymers based on a naphthalenediimide (NDI) acceptor (A) unit and three different donor (D) units with varied electron-donating strength including thiophene (P(NDI-T)), thieno[3,2-b]thiophene (P(NDI-TT)), and thieno[3,2-b;4,5-b]dithiophene (P(NDI-TDT)), were synthesized, for the application as acceptor materials in all-polymer solar cells (all-PSCs). The effect of the donor units of thiophene, thienothiophene (TT) and thienodithiophene (TDT) on the physicochemical and photovoltaic properties of the n-type D-A copolymers was systematically investigated. It was found that the absorption spectrum is red-shifted and the energy band gap (Eg ) is reduced for the NDI-based D-A copolymers with increasing number of thiophene rings in the thiophene or fused thiophene donor units. All-PSCs were fabricated with the medium band gap conjugated polymer J51 (Eg of ca 1.9 eV) as polymer donor and the n-type D-A copolymers as acceptor. The power conversion efficiency reached 2.59 %, 3.70 % and 5.10 % for the all-PSCs with P(NDI-T), P(NDI-TT), and P(NDI-TDT) as acceptor, respectively. The results indicate that a larger conjugated fused molecular plane with more thiophene rings as donor units in the NDI-based D-A copolymers is beneficial to reduce the band gap, broaden the absorption and enhance the photovoltaic performance of n-type D-A copolymer acceptors.

Worker nodes on the grid exhibit great diversity, making it difficult to offer uniform processing resources. A pilot job architecture, which probes the environment on the remote worker node before pulling down a payload job, can help. Pilot jobs become smart wrappers, preparing an appropriate environment for job execution and providing logging and monitoring capabilities. PanDA (Production and Distributed Analysis), an ATLAS and OSG workload management system, follows this design. However, in the simplest (and most efficient) pilot submission approach of identical pilots carrying the same identifying grid proxy, end-user accounting by the site can only be done with application-level information (PanDA maintains its own end-user accounting), and end-user jobs run with the identity and privileges of the proxy carried by the pilots, which may be seen as a security risk. To address these issues, we have enabled PanDA to use gLExec, a tool provided by EGEE which runs payload jobs under an end-user's identity. End-user proxies are pre-staged in a credential caching service, MyProxy, and the information needed by the pilots to access them is stored in the PanDA DB. gLExec then extracts from the user's proxy the proper identity under which to run. We describe the deployment, installation, and configuration of gLExec, and how PanDA components have been augmented to use it. We describe how difficulties were overcome, and how security risks have been mitigated. Results are presented from OSG and EGEE Grid environments performing ATLAS analysis using PanDA and gLExec.

Initially we established that the binding of collagen to human blood platelets stimulates both the rapid loss of PIP2 and the generation of inositol-4,5-bisphosphate (IP2) and inositol-1,4,5-triphosphate (IP3). These results indicate that the binding of collagen stimulates inositol phospholipid-specific phospholipase C during platelet activation. The fact that GTP or GTP-gamma-S augments, and pertussis toxin inhibits, collagen-induced IP3 formation suggests that a GTP-binding protein or (or proteins) may be directly involved in the regulation of phospholipase C-mediated phosphoinositide turnover in human platelets. We have used several complementary techniques to isolate and characterize a platelet 41-kDa polypeptide (or polypeptides) that has a number of structural and functional similarities to the regulatory alpha i subunit of the GTP-binding proteins isolated from bovine brain. This 41-kDa polypeptide (or polypeptides) is found to be closely associated with at least four membrane glycoproteins (e.g., gp180, gp110, gp95, and gp75) in a 330-kDa complex that can be dissociated by treatment with high salt plus urea. Most important, we have demonstrated that antilymphoma 41-kDa (alpha i subunit of GTP-binding proteins) antibody cross-reacts with the platelet 41-kDa protein (or proteins) and the alpha i subunit of bovine brain Gi alpha proteins, and blocks GTP/collagen-induced IP3 formation. These data provide strong evidence that the 41-kDa platelet GTP-binding protein (or proteins) is directly involved in collagen-induced signal transduction during platelet activation.

A sunken soft-spot or fontanel is a sign for dehydration in infants. Around the world, folk illnesses, such as caída de la mollera in some Latin American cultures, often incorporate this sign as a hallmark of illness, but may or may not incorporate re-hydration therapies in treatment strategies. This report describes a study of lay descriptions of causes, symptoms, and treatments for caída de la mollera in three diverse Latin American populations. A mixed-methods approach was used. Representative community-based samples were interviewed in rural Guatemala, Guadalajara, Mexico, and Edinburgh, Texas, with a 132 item questionnaire on the causes, susceptibility, symptoms, and therapies for caída de la mollera. Cultural consensus analysis was used to estimate community beliefs about caída. Interviews conducted in rural Guatemala (n = 60), urban Mexico (n = 62), and rural Texas on the Mexican border (n = 61) indicated consistency in thematic elements within and among these three diverse communities. The high degree of consistency in the illness explanatory models indicated shared beliefs about caída de la mollera in each of the communities and a core model shared across communities. However, an important aspect of the community beliefs was that rehydration therapies were not widely endorsed. The consistency in explanatory models in such diverse communities, as well as the high degree of recognition and experience with this illness, may facilitate communication between community members, and health care providers/public health intervention planners to increase use of rehydration therapies for caída de la mollera. Recommendations for culturally informed and respectful approaches to clinical communication are provided.

Brucella melitensis is an organism of paramount zoonotic importance. The 28 kDa outer membrane protein (OMP) is one of the immunodominant antigens of B. melitensis. The gene encoding 28 kDa OMP (omp28) has been amplified from B. melitensis Rev. 1 strain. A PCR product of 753 bp, encoding complete omp28 gene of B. melitensis, was obtained. The gene was further cloned and sequenced. The nucleotide sequence of B. melitensis Rev. 1 strain showed substitution of 2 nucleotides from that of 16M strain.

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous administration of the drug (50 mg/kg of body weight) to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF rats). The impaired kidney function was observed in U-ARF rats on the basis of physiological parameters observed by microscopy of the kidney and obtained by chemical analysis of the plasma. After a 1-min intravenous infusion of DA-1131, the concentrations in plasma and the total area under the plasma concentration-time curve from time zero to time infinity increased significantly in U-ARF rats compared with those in control rats (13,000 versus 4,400 μg · min/ml). This was due to the significantly slower total body clearance (CL) of DA-1131 (3.84 versus 11.4 ml/min/kg) from U-ARF rats than from control rats. The significantly slower CL of DA-1131 from U-ARF rats was due to both significantly slower renal clearance (0.000635 versus 4.95 ml/min/kg because of a significant decrease in the 8-h urinary excretion of unchanged DA-1131 [1.54 versus 43.8% of the intravenous dose] due to impaired kidney function, as proved by the significant decrease in creatinine clearance [0.0159 versus 4.29 ml/min/kg]) and significantly slower nonrenal clearance (3.80 versus 6.34 ml/min/kg because of a significant decrease in the metabolism of DA-1131 in the kidney) in U-ARF rats. The amounts of DA-1131 recovered from all tissues studied (except the kidneys) were significantly higher for U-ARF rats than for control rats; however, the ratios of the amount in tissue to the concentration in plasma (except those for the kidney, small intestine, and spleen) were not significantly different between the two groups of rats, indicating that the affinity of DA-1131 for rat tissues was not changed considerably in

Spectroscopic observations of the wide binary L151-81A/B reveal that both components are white dwarfs with spectral types DB3 and DA4, the first such binary identified in a comprehensive survey of Luyten and Giclas common proper motion pairs. Assuming log g = 8, measurements of the helium line profiles in the DB primary yield Teff = 16,000 + or - 2,000, while the hydrogen profiles for the DA companion yield Teff =12,000 + or - 2,000. The existence of a helium-rich/hydrogen-rich degenerate pair offers several interesting tests of theoretical white dwarf formation channels and surface abundance evolution.

Activation of dopaminergic (DA) systems is a necessary component of the behavior effects of d-amphetamine, but other neurotransmitters such as norepinephrine (NE) and serotonin (5-HT) appear to modulate DA input; thus, they might have an important role in the stimulus (subjective) effects of this drug. Therefore, rats were trained to discriminate d-amphetamine (1 mg/kg) from saline and given combination (antagonism, potentiation) or substitution (generalization) tests with drugs that act through DA, noradrenergic, or serotonergic (5-HT) mechanisms. In the first of two experiments, the D1 antagonist SCH 39166 blocked the effects of d-amphetamine (1 mg/kg) at doses of 0.05, 0.1, and 0.2 mg/kg. NE and 5-HT antagonists including prazosin (0.5-2 mg/kg), idazoxan (1.25-5 mg/kg), ketanserin (0.06-0.15 mg/kg), and metergoline (5-20 mg/kg) had no significant effects on the d-amphetamine cue. In the second experiment, neither the alpha 2-NE agonist clonidine (0.0025-0.1 mg/kg), the beta-NE agonist salbutamol (0.05-0.25 mg/kg), nor the NE uptake inhibitor nisoxetine (5-15 mg/kg) had d-amphetamine-like effects. The alpha 2-NE antagonist yohimbine (0.5-2 mg/kg) and the beta-NE antagonist propranolol (0.5-3 mg/kg) failed to alter the d-amphetamine cue. ICS 205-930 (10 mg/kg) neither mimicked nor blocked the effects of 1 mg/kg of d-amphetamine. Indeed, this 5-HT3 antagonist potentiated the actions of lower doses of d-amphetamine (0.25-0.4 mg/kg); the potentiation of the 0.25-mg/kg dose was blocked significantly by the alpha 1-NE antagonist prazosin (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

While white dwarf stars are classified into many subgroups based on the appearance of hydrogen, helium, carbon, oxygen and other spectral lines - or even pure continuum with no lines in the case of the DC stars - the vast majority fall into two major subgroups: those with hydrogen atmospheres (the DA white dwarfs), and those with helium atmospheres (the DO and DB white dwarfs). Remarkably, in the range 45000 >= Teff >= 30000K there are only a few white dwarfs with helium atmospheres to be found - the vast majority are DAs in this temperature range - although white dwarfs with helium atmospheres are found at both hotter (DO) and cooler (DB) effective temperatures. This dearth of helium atmosphere white dwarfs in this temperature range is known as the `DB gap' and is understood in terms convective mixing of the outer atmospheres at the hot and cool ends of the gap, while radiative stability allows the lighter hydrogen to float to the top in the DB gap, so the stars are seen to be DA hydrogen atmosphere white dwarfs. Asteroseismology is an important tool for probing stellar interiors, and white dwarf stars are the most successfully studied group using this technique. In a stability analysis of the stars in the DB gap, Shibahashi has recently predicted the existence of a new class of pulsating white dwarf stars. He finds from models that DA white dwarfs near the red edge of the DB gap have convectively stable outer atmospheres because of a steep mean molecular weight gradient, yet nevertheless have a superadiabatic layer that renders them pulsationally unstable due to radiative heat exchange. There have been very few observational tests for pulsation among stars of this type. We have initiated a survey to search for the predicted pulsators and report here our first observations of five stars with the South African Astronomical Observatory 1.9-m telescope and University of Cape Town CCD photometer, and two stars with the William Herschel Telescope 4.2-m telescope and

Serra da Estrela is the highest mountain in Portugal (1,993 m ASL) and part of the Iberian Central Cordillera. The mountain has a strong relief and a lithological diversity with several types of granitoids and metasediments. Most of the western plateau area was glaciated during the Last Glacial Maximum and its morphology is dominated by glacial landforms. Vieira (2004) produced a detailed geomorphological map of Serra da Estrela and described several sites showing stratified slope, head and debris-flow deposits. Based on the geomorphological analysis of the relationships between glacial and periglacial evidence, a first relative chronology was presented. However, a detailed and systematical sedimentological analysis has not been conducted before and absolute ages are also lacking. Micromorphology analysis has proven to be of considerable value in the interpretation of mountain soils and sediments. Such interpretation depends on identifying diagnostic features, indicating factors as the presence or absence of permafrost, thickness of the active layer, ice segregation and the operation of processes of mass-wasting. In this study, micromorphology was used to answer questions concerning the composition, structure, origin and depositional processes of relict slope deposits. Micromorphology allowed a systematic description of the physical characteristics of the sediments. Lamination and sorting, when preserved, are good evidence for overland flow. Features due to deformation (folds, boudins, coatings and tails due to the rotation of clasts) are associated with sliding. Other mass-movements such as debris flows, earth flows, and to a certain extent, dry grain flows may be characterized by similar microscopic facies, typically a poorly sorted, porphyric material. Porosity gives evidence for both liquefaction (debris flows) and frost-induced mass-movement (solifluction). The relict slope deposits of the Serra da Estrela show an increase in cryogenic micromorphological

One of the challenges in the analysis of large data sets, particularly in a population-based setting, is the ability to perform comparisons across projects. This has to be done in such a way that the integrity of each individual project is maintained, while ensuring that the data are comparable across projects. These issues are beginning to be observed in human DNA methylation studies, as the Illumina 450k platform and next generation sequencing-based assays grow in popularity and decrease in price. This increase in productivity is enabling new insights into epigenetics, but also requires the development of pipelines and software capable of handling the large volumes of data. The specific problems inherent in creating a platform for the storage, comparison, integration, and visualization of DNA methylation data include data storage, algorithm efficiency and ability to interpret the results to derive biological meaning from them. Databases provide a ready-made solution to these issues, but as yet no tools exist that that leverage these advantages while providing an intuitive user interface for interpreting results in a genomic context. We have addressed this void by integrating a database to store DNA methylation data with a web interface to query and visualize the database and a set of libraries for more complex analysis. The resulting platform is called DaVIE: Database for the Visualization and Integration of Epigenetics data. DaVIE can use data culled from a variety of sources, and the web interface includes the ability to group samples by sub-type, compare multiple projects and visualize genomic features in relation to sites of interest. We have used DaVIE to identify patterns of DNA methylation in specific projects and across different projects, identify outlier samples, and cross-check differentially methylated CpG sites identified in specific projects across large numbers of samples. A demonstration server has been setup using GEO data at http

The diverse physiological effects of dopamine are mediated by multiple receptor systems. The dDA1 represents one of the Drosophila dopamine receptors that activate the cAMP cascade. To gain insight into the role of dDA1, we generated a polyclonal antibody against the unique sequence in dDA1 and investigated dDA1 distribution in the central nervous system (CNS) of Drosophila melanogaster. In both larval and adult CNS pronounced dDA1 immunoreactivity was present in the neuropil of the mushroom bodies, a brain structure crucial for learning and memory in insects, and four unpaired neurons in each thoracic segment. In addition, the larval abdominal ganglion contained two dDA1 cells in each segment. This expression pattern appeared to be maintained in the condensed adult abdominal ganglion although the precise number and the intensity of staining were somewhat variable. The adult CNS also exhibited intense dDA1 immunoreactivity in the central complex, a structure controlling higher-order motor function, moderate expression in several neurosecretory cells, and weak staining in two unpaired neurons in the mesothoracic neuromere. The dDA1 expression in these areas was only detected in adult, but not in third instar larval CNS.

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

Cholinergic neurons express choline acetyltransferase (ChAT) which synthesizes acetylcholine. We show here for the first time that primate-specific 82-kDa ChAT is expressed in nuclei of cholinergic neurons in human brain and spinal cord; isoform-specific antibodies were used to compare localization patterns and temporal expression of the more abundant 69-kDa ChAT and primate-specific 82-kDa ChAT in necropsy tissues. The 82-kDa ChAT co-localizes with 69-kDa ChAT in well-characterized cholinergic areas, but is also found in the claustrum which does not contain 69-kDa ChAT. Cholinergic neuron function changes with increasing age and are targeted in neurodegenerative diseases such as AD, thus we compared expression and subcellular localization of 69- and 82-kDa ChAT in necropsy brain samples from control subjects of varying ages and from Alzheimer disease (AD) subjects. The 82-kDa ChAT protein was expressed in cholinergic neurons in brain from birth until the eighth decade of life and in AD, but the subcellular staining pattern and proportion of neurons that were immunopositive changed with increasing age and in AD.

The cleavage stimulation factor (CstF), and the cleavage and polyadenylation specificity factor (CPSF) are necessary for 3'-terminal processing of polyadenylated mRNAs. To study the distribution of 3' cleavage factors in the nuclei of human T24 cells, monoclonal antibodies against the CstF 64 kDa subunit and against the CPSF 100 kDa subunit were used for immunofluorescent labelling. CstF 64 kDa and CPSF 100 kDa were distributed in a fibrogranular pattern in the nucleoplasm and, in addition, were concentrated in 1-4 bright foci. Double immunofluorescence labelling experiments revealed that the foci either overlapped with, or resided next to, a coiled body. Inhibition of transcription with alpha-amanitin or 5,6-dichloro-beta-D-ribofuranosyl-benzimidazole (DRB) resulted in the complete co-localization of coiled bodies and foci containing 3' cleavage factors. Electron microscopy on immunogold double-labelled cells revealed that the foci represent compact spherical fibrous structures, we named 'cleavage bodies', intimately associated with coiled bodies. We found that approximately 20% of the cleavage bodies contained a high concentration of newly synthesized RNA, whereas coiled bodies were devoid of nascent RNA. Our results suggest that the cleavage bodies that contain RNA are those that are adjacent to a coiled body. These findings reveal a dynamic and transcription-dependent interaction between different subnuclear domains, and suggest a relationship between coiled bodies and specific transcripts. Images PMID:8654386

Describes and analyzes the language of young people in Italy today. Particular focus is on the expressions using "para" (e.g., "in para totale" = to be very bored or worried) and the phrase "una cosa da panico" (something terrible or its opposite something wonderful). (CFM)

Patients with pemphigus may produce antibodies against molecules other than the classical transmembranal ones. Recently, for example antibodies to 230 kDa antigens have been found in association with antibodies to intercellular substance. To better understand their prevalence, clinical correlates and prognostic significance of bands other than 130 and 160 kDa, we studied 67 pemphigus sera. About one-fourth of patients revealed multiple heterogeneous bands and 13% the 230 kDa band. When challenged with the recombinant protein rBP55, the carbossiterminal portion of bullous pemphigoid major antigen, all 230 kDa-positive-sera proved negative. Caution is to be recommended in interpreting pemphigus sera with a band migrating at the 230 kDa level.

A 130 kDa PLC isozyme was purified from the particulate fraction of bovine cerebellum. This PLC was recognized by a polyclonal antiserum generated against the purified 97 kDa PLC-beta 4. Reconstitution of the purified 130 kDa PLC with the membranes of C6 Bu-1 cells in the presence of GTP gamma S or AlF4- resulted in PLC activation as well as the association of PLC with the membranes. Both the association and activation were revoked when the membrane was washed with 2 M KCl. The 97 kDa PLC-beta 4 did not associate with membranes. These data suggest that the 130 kDa PLC is the intact form of PLC-beta 4 the activity of which is likely to be regulated by a G-protein on the membrane.

In the first half of the fourteenth century, Niccolò da Reggio translated more than fifty works by Galen from Greek into Latin, and by mid-century most if not all of them had reached the papal court at Avignon, where Guy de Chauliac praised their accuracy and cited them regularly in his Great Surgery of 1363. Yet contemporary physicians at nearby Montpellier almost never referred to them, ordinarily preferring to quote from the older Arabic-Latin translations. Examining a particular context, the ways in which urological conditions were described in the old and new versions of Galen, suggests that medical teachers and commentators may have found it difficult to give up the familiarity of the traditional language in favor of Niccolò's new terminology.

A truncated fragment of the gene encoding the 200-kDa protein (P200) of Babesia bigemina was cloned into a plasmid vector, pGEX-4 T-1 and expressed in Escherichia coli as a glutathione-S-transferase fused protein. An indirect enzyme-linked immunosorbent assay (ELISA) using the rp200/CT detected specific antibodies in cattle experimentally infected with B. bigemina. Furthermore, the antigen did not cross-react with antibodies to Babesia bovis, a closely related Babesia parasite indicating that rp200/CT is a specific antigen for the diagnosis of B. bigemina infection. Additionally, ELISA using p200/CT and polymerase chain reaction were conducted on serum and corresponding DNA samples obtained from field cattle to evaluate the diagnostic utility of the p200/CT antigen. Results from the current study suggest that p200/CT ELISA is a sensitive and specific method for improved serodiagnosis of B. bigemina infection.

The Einstein Observatory's imaging proportional counter has detected 150-eV soft X-ray radiation from the four hot DA white dwarfs EG 187, Gr 288 and 289, and LB 1663. The observed pulse height spectra suggest that the emission is generated by hot photospheres whose T(eff) lie in the 30,000-60,000 K range. The IUE spacecraft UV spectra and H-beta line profiles for the four stars have been fitted, along with the X-ray fluxes, with a grid of hot, high gravity, homogeneous model atmospheres of mixed H-He composition. In all cases, the data require the presence of some X-ray opacity in the photosphere. Attention is given to the implications of this result in the context of white dwarf surface layer diffusion theories. Also noted are the limits imposed on the hot white dwarf population by the Einstein Medium Sensitivity Survey.

The faint (g = 16.9) hot white dwarf BOKS 53856 was observed by the Kepler Mission in short cadence mode during mid-2009. Analysis of these observations reveals a highly stable modulation with a period of 6.1375 hr and a 2.46% half-amplitude. The folded light curve has an unusual shape that is difficult to explain in terms of a binary system containing an unseen companion more luminous than an L0 brown dwarf. Optical spectra of BOKS 53856 show a T{sub eff} = 34,000 K, log g = 8.0 DA white dwarf. There are few, if any, known white dwarfs in this temperature range exhibiting photometric variations similar to those we describe. A magnetic spin-modulated white dwarf model can in principle explain the light curve, an interpretation supported by spectral observations of the H{alpha} line showing evidence of Zeeman splitting.

Antitumor, antimicrobial and antioxidant activities of basil were studied, along with its characterization in phenolic compounds, organic acids and soluble sugars. The results placed basil as a valuable candidate for functionalization and conservation of food products, maintaining their nutritional properties, while increasing their shelf life and potential health effects. The basil leaves were then incorporated in "Serra da Estrela Cheese", either in its dehydrated form or as a decoction. The cheeses were then subject to a nutritional evaluation, being characterized for their fatty acids, minerals and CIE color parameters. To assess the combined effects of plant incorporation and storage time, a 2-way ANOVA was used to process the results, further analysed through a linear discriminant analysis. Overall, basil leaves provided antioxidant activity to the cheeses, reduced the moisture, and preserved the unsaturated fatty acids and proteins. Comparing both incorporation types, the decoctions had a higher functionalizing and conservative effect.

PG 0948+534 is currently one of the hottest DA white dwarf stars, and is also one of the most mysterious. Attempts to model the sharp, deep absorption features of this star have been unsuccessful. In these proceedings we describe our analysis of PG 0948+534. We perform a line survey of the UV spectrum of PG 0948+534, making detections of 300+ absorption features, and identifying four distinct velocity regimes. We find evidence of circumstellar absorption in the profiles of C IV and Si IV. Using non-local thermodynamic equilibrium model atmospheres, we are able to correctly model the absorption features of the star, providing abundance measurements for C, N, O, and Si for PG 0948+534 for the first time. We also revise the effective temperature and gravity for this star using models including these new abundances.

This paper offers a commentary on three aspects of the Supreme Court’s recent decision (2011Da22092). First, contrary to the Court’s finding, this paper argues that epidemiological evidence can be used to estimate the probability that a given risk factor caused a disease in an individual plaintiff. Second, the distinction between specific and non-specific diseases, upon which the Court relies, is shown to be without scientific basis. Third, this commentary points out that the Court’s finding concerning defect of expression effectively enables tobacco companies to profit from the efforts of epidemiologists and others involved in public health to raise awareness of the dangers of smoking. PMID:26063352

Following the discovery of discoloration on some pages of the Atlantic Codex (AC) of Leonardo da Vinci kept in the Biblioteca Ambrosiana in Milan, some investigations have been carried out to verify the presence of microorganisms, such as bacteria and fungi. To verify the presence of microorganisms a noninvasive method of sampling has been used that was efficient and allowed us to highlight the microbial facies of the material that was examined using conventional microbiological techniques. The microclimatic conditions in the storage room as well as the water content of the volume were also assessed. The combined observations allowed the conclusion that the discoloration of suspected biological origin on some pages of AC is not related to the presence or current attack of microbial agents. PMID:25574171

Following the discovery of discoloration on some pages of the Atlantic Codex (AC) of Leonardo da Vinci kept in the Biblioteca Ambrosiana in Milan, some investigations have been carried out to verify the presence of microorganisms, such as bacteria and fungi. To verify the presence of microorganisms a noninvasive method of sampling has been used that was efficient and allowed us to highlight the microbial facies of the material that was examined using conventional microbiological techniques. The microclimatic conditions in the storage room as well as the water content of the volume were also assessed. The combined observations allowed the conclusion that the discoloration of suspected biological origin on some pages of AC is not related to the presence or current attack of microbial agents.

The career of Henrique da Rocha Lima is closely linked to cultural and scientific relations between Brazil and Germany. He pursued his scientific work at biomedical research institutions in both countries, but it was in Germany that he attained international standing, thanks to his research in the fields of microbiology, pathology and tropical medicine. His prestige and active participation in both Brazil's and Germany's scientific communities meant he was able to further academic interchange between both nations, mobilizing many people and institutions to contribute to this process. I present the obstacles and challenges faced in studying this complex character, whose career sheds light on the machinations of international scientific relations and some socio-historical processes that marked the institutionalization of science in Brazil.

The first robotic simple hysterectomy was performed more than 10 years ago. These days, robotic-assisted hysterectomy is accepted as an alternative surgical approach and is applied both in benign and malignant surgical entities. The two important points that should be taken into account to optimize postoperative outcomes in the early period of a surgeon’s training are how to achieve optimal oncological and functional results. Overcoming any technical challenge, as with any innovative surgical method, leads to an improved surgical operation timewise as well as for patients’ safety. The standardization of the technique and recognition of critical anatomical landmarks are essential for optimal oncological and clinical outcomes on both simple and radical robotic-assisted hysterectomy. Based on our experience, our intention is to present user-friendly tips and tricks to optimize the application of a da Vinci® robot in simple or radical hysterectomies. PMID:27403078

Nurses today are facing an ever changing health care system. Stimulated by health care reform and limited resources, nursing education is being challenged to prepare nurses for this uncertain environment. Looking to the past can offer possible solutions to the issues nursing education is confronting. Seven principles of da Vincian thinking have been identified (Gelb, 2004). As a follow-up to an exploration of the curiosità principle (Butts & Story, 2013), this article will explore the three principles of dimostrazione, sfumato, and corporalita. Nursing faculty can set the stage for a meaningful educational experience through these principles of demonstration (dimostrazione), uncertainty (sfumato), and cultivation (corporalita). Preparing nurses not only to manage but also to flourish in the current health care environment that will enhance the nurse's and patient's experience.

Additional Middle Paleolithic human remains from layers 17, 18, and 22 of the Gruta da Oliveira, Portugal consist of a proximal manual phalanx 2 (Oliveira 5), a partial postcanine tooth (Oliveira 6), a humeral diaphysis (Oliveira 7), a distal mandibular molar (Oliveira 8), and a mandibular premolar (P(3) ) (Oliveira 9). Oliveira 5, 6, and 8 are unremarkable for Late Pleistocene humans. The Oliveira 7 right humerus is moderately robust or the individual had the stocky body proportions of other European (including Iberian) Neandertals. The Oliveira 9 P(3) has a large and symmetrical crown and lacks a distal accessory ridge and accessory lingual cusps, overlapping both Neandertal and recent human ranges of variation. It contrasts with at least recent human P(3) s in having relatively thin enamel. These join the Oliveira 1 to 4 remains in further documenting early MIS 3 Neandertal morphology in western Iberia.

An international VLBI experiment on radio location of the asteroid 2012 DA14 was organized on 2013 February 15--16, during its flyby close to Earth. The purpose of observations was to investigate and specify orbital parameters of the asteroid, as well as to evaluate its rotation period and other characteristics. The irradiation of the asteroid was performed by the RT-70 transmitter at Evpatoria (Crimea, Ukraine), while the reflected signals were successfully accepted by the two 32 m radio telescopes at Medicina (Bologna, Italy) and Irbene (Ventspils, Latvia). Processing and interpretation of the data were performed both in the Radiophysical Research Institute and in the Ventspils International Radio Astronomy Center. The first results of this experiment are presented and discussed.

Intraerythrocytic parasites degrade haemoglobin to make available nutrients for their growth and maturation. Plasmepsins, the aspartic proteases of Plasmodium play a significant role in haemoglobin degradation and are proposed as attractive drug targets. In the present study the gene which encodes plasmepsin in rodent malaria parasite, Plasmodium berghei, was cloned and expressed. The gene was sequenced and expressed in Escherichia coli BL21DE3 and a recombinant plasmepsin of molecular weight 43 kDa was obtained. The sequence obtained was analysed and compared with plasmepsins of other Plasmodium spp. Mice immunized with the recombinant plasmepsin induced a strong humoral immune response. ELISA and IFA performed on the serum of immunized mice showed high antibody titres. Along with this, in vivo study exhibited partial protection against P. berghei infection suggesting role of plasmepsin in malaria control.

Top-down proteomics is capable of identifying and quantitating unique proteoforms through the analysis of intact proteins. We extended the coverage of the label-free technique, achieving differential analysis of whole proteins <30 kDa from the proteomes of growing and senescent human fibroblasts. By integrating improved control software with more instrument time allocated for quantitation of intact ions, we were able to collect protein data between the two cell states, confidently comparing 1577 proteoform levels. To then identify and characterize proteoforms, our advanced acquisition software, named Autopilot, employed enhanced identification efficiency in identifying 1180 unique Swiss-Prot accession numbers at 1% false-discovery rate. This coverage of the low mass proteome is equivalent to the largest previously reported but was accomplished in 23% of the total acquisition time. By maximizing both the number of quantified proteoforms and their identification rate in an integrated software environment, this work significantly advances proteoform-resolved analyses of complex systems.

The influence of the work of Dr. Guillermo Contreras Da Silva and his colaborators on the evolution of microbiology in Chile is briefly analyzed. Dr. Contreras was trained in modern virology at Yale University with Dr. J. Melnick under the sponsorhip of the Rockefeller Foundation. During this training, he used serological methods to classify Cocksakie viruses. After his return to Chile, he studied the epidemiology of enteroviruses, including poliovirus. His laboratory, the country's first in modern virology, took an active role in Chile's first Sabin polio vaccination in 1961. Dr. Contreras and his group transformed the teaching and the character of microbiology in Chile from a descriptive medically oriented discipline into an autonomous, quantitative and experimental science. They modernized microbiology with the introduction of molecular biology and microbial genetics and fostered collaborations with allied biological sciences. Dr. Contreras was a Guggenheim Fellow, and until his retirement, was the Chief of the Viral Products Division, Bureau of Biologies, Ottawa, Canada.

The smile of the famed portrait 'The Mona Lisa' has perplexed both art historians and researchers for the past 500 years. There has been a multitude of theories expounded to explain the nature of the model's enigmatic smile. The origin of the model's wry smile can be demonstrated through a careful analysis of both documented facts concerning the portrait--some gathered only recently through the use of modern technology--and a knowledge of the clinical presentation of Bell's palsy. Bell's palsy is more prevalent in women who are either pregnant or who have recently given birth. This paper postulates that the smile of the portrait's model was due to Leonardo da Vinci's anatomically precise representation of a new mother affected by Bell's palsy subsequent to her recent pregnancy.

Leonardo da Vinci (1452-1519) incorporates the symbiosis of art and medicine and can be addressed as the founder of medical illustration in the time of the Renaissance. His anatomy studies were not published in his time, which explains why Leonardo's outstanding knowledge of anatomy, physiology, and medicine had no impact on his scientific contemporaries and is therefore primarily of retrospective importance in the history of medicine. The collection of anatomical illustrations remained unknown until their rediscovery in the eighteenth century and their wide publication at the beginning of our century. This article systematically reviews Leonardo's genitourinary drawings with regard to urodynamic aspects of the upper and lower urinary tract, highlighting topics such as vesicoureteral reflux and urinary sphincter mechanisms.

The aromatic hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop-helix-PAS protein which forms a heterodimer with aromatic hydrocarbon receptor (AHR), this heterodimer mediating the signal transduction in response to the various xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and directly interacting with target genes by binding to xenobiotic responsive elements. An anti-ARNT antibody was raised in rabbits against the bacterially expressed ARNT of amino acids 21-328 from the N-terminal. Using this antibody, besides ARNT itself, we detected at least one protein, 120 kDa, in the immunoprecipitate of anti-ARNT antibodies in HepG2 cells as well as in Hepa-1 cells. However, this protein is not present in the immunoprecipitate of the anti-AHR antisera nor in that of the preimmune sera of the rabbits used for the immunization.

The 70 kDa heat shock protein (Hsp70) is synthesized in response to a variety of stresses, including ischemia, and is thought to act as a molecular chaperone to prevent protein denaturation and facilitate protein folding. Matrix metalloproteinases (MMPs), a family of serine proteases, are also upregulated by ischemia and are thought to promote cell death and tissue injury. We examined the influence of Hsp70 on expression and activity of MMPs. Astrocyte cultures were prepared from neonatal mice and transfected with retroviral vectors containing hsp70 or lacZ or mock infected, then exposed to oxygen-glucose deprivation followed by reperfusion. Zymograms and Western blots showed that Hsp70 over-expression suppressed MMP-2 and MMP-9. These findings suggest that Hsp70 may protect by regulating MMPs.

A novel prothrombin activator enzyme, which we have named 'berythractivase', was isolated from Bothrops erythromelas (jararaca-da-seca) snake venom. Berythractivase was purified by a single cation-exchange-chromatography step on a Resource S (Amersham Biosciences) column. The overall purification (31-fold) indicates that berythractivase comprises about 5% of the crude venom. It is a single-chain protein with a molecular mass of 78 kDa. SDS/PAGE of prothrombin after activation by berythractivase showed fragment patterns similar to those generated by group A prothrombin activators, which convert prothrombin into meizothrombin, independent of the prothrombinase complex. Chelating agents, such as EDTA and o -phenanthroline, rapidly inhibited the enzymic activity of berythractivase, like a typical metalloproteinase. Human fibrinogen A alpha-chain was slowly digested only after longer incubation with berythractivase, and no effect on the beta- or gamma-chains was observed. Berythractivase was also capable of triggering endothelial proinflammatory and procoagulant cell responses. von Willebrand factor was released, and the surface expression of both intracellular adhesion molecule-1 and E-selectin was up-regulated by berythractivase in cultured human umbilical-vein endothelial cells. The complete berythractivase cDNA was cloned from a B. erythromelas venom-gland cDNA library. The cDNA sequence possesses 2330 bp and encodes a preproprotein with significant sequence similarity to many other mature metalloproteinases reported from snake venoms. Berythractivase contains metalloproteinase, desintegrin-like and cysteine-rich domains. However, berythractivase did not elicit any haemorrhagic response. These results show that, although the primary structure of berythractivase is related to that of snake-venom haemorrhagic metalloproteinases and functionally similar to group A prothrombin activators, it is a prothrombin activator devoid of haemorrhagic activity. This is a feature

This study explored the rather rapid adoption of a new surgical device - the da Vinci robot - in the Netherlands despite the high costs and its controversial clinical benefits. We used the concept 'affordances' as a conceptual-analytic tool to refer to the perceived promises, symbolic meanings, and utility values of an innovation constructed in the wider social context of use. This concept helps us empirically understand robot adoption. Data from 28 in-depth interviews with diverse purposively-sampled stakeholders, and from medical literature, policy documents, Health Technology Assessment reports, congress websites and patients' weblogs/forums between April 2009 and February 2014 were systematically analysed from the perspective of affordances. We distinguished five interrelated affordances of the robot that accounted for shaping and fulfilling its rapid adoption: 'characteristics-related' affordances such as smart nomenclature and novelty, symbolising high-tech clinical excellence; 'research-related' affordances offering medical-technical scientific excellence; 'entrepreneurship-related' affordances for performing better-than-the-competition; 'policy-related' affordances indicating the robot's liberalised provision and its reduced financial risks; and 'communication-related' affordances of the robot in shaping patients' choices and the public's expectations by resonating promising discourses while pushing uncertainties into the background. These affordances make the take-up and use of the da Vinci robot sound perfectly rational and inevitable. This Dutch case study demonstrates the fruitfulness of the affordances approach to empirically capturing the contextual dynamics of technology adoption in health care: exploring in-depth actors' interaction with the technology while considering the interpretative spaces created in situations of use. This approach can best elicit real-life value of innovations, values as defined through the eyes of (potential) users.

An interesting question in maize development is why only a single zein gene is highly expressed in each of the 19-kDa zein gene clusters (A and B types), z1A2-1 and z1B4, in the immature endosperm. For instance, epigenetic marks could provide a structural difference. Therefore, we investigated the DNA methylation of the arrays of gene copies in both promoter and gene body regions of leaf (non-expressing tissue as a control), normal endosperm, and cultured endosperm. Although we could show that expressed genes have much lower methylation levels in promoter regions than silent ones in both leaf and normal endosperm, there was surprisingly also a difference in the pattern of the z1A and z1B gene clusters. The expression of z1B gene is suppressed by increased DNA methylation and activated with reduced DNA methylation, whereas z1A gene expression is not. DNA methylation in gene coding regions is higher in leaf than in endosperm, whereas no significant difference is observed in gene bodies between expressed and non-expressed gene copies. A median CHG methylation (25–30%) appears to be optimal for gene expression. Moreover, tissue-cultured endosperm can reset the DNA methylation pattern and tissue-specific gene expression. These results reveal that DNA methylation changes of the 19-kDa zein genes is subject to plant development and tissue culture treatment, but varies in different chromosomal locations, indicating that DNA methylation changes do not apply to gene expression in a uniform fashion. Because tissue culture is used to produce transgenic plants, these studies provide new insights into variation of gene expression of integrated sequences. PMID:26741504

The platelet-derived growth factor (PDGF) stimulated the phosphorylation of a nuclear protein of 64 kDa (pp64) in nuclei of nontransformed normal rat kidney (NRK) cells. Low levels of phosphorylation of pp64 were observed in nuclei of serum-starved NRK cells. Fetal calf serum (FCS), PDGF, and homodimeric v-sis and PDGF A-chain protein enhanced the incorporation of 32P into pp64 over 4-fold within 30 min and over 8-fold within 2 h of exposure of NRK cells to the growth factors. In contrast, constitutive phosphorylation of 32P-labeled pp64 in nuclei of NRK cells transformed by the simian sarcoma virus (SSV) was high and only minimally stimulated by PDGF and FCS. 32P-Labeled pp64 was isolated from nuclei of PDGF-stimulated nontransformed NRK cells; the 32P of pp64 was labile in 1 M KOH, and pp64 was not significantly recognized by anti-phosphotyrosine antisera, suggesting that the PDGF-induced phosphorylation of pp64 occurred on serine or on threonine residues. However, pp64 from SSV-transformed NRK cell nuclei was significantly stable to base hydrolysis and was immunoprecipitated with anti-phosphotyrosine antisera, suggesting that pp64 from SSV-transformed cell nuclei is phosphorylated also on tyrosine. FCS, PDGF, and PDGF A- and B-chain homodimers thus stimulate the rapid time-dependent phosphorylation of a 64-kDa nuclear protein shortly after stimulation of responsive cells. The growth factor-stimulated phosphorylation of pp64 and the constitutive high levels of pp64 phosphorylation in cells transformed by SSV suggest important roles for pp64 and perhaps regulated nuclear protein kinases and phosphatases in cell division and proliferation.

CoDa (Cosmic Dawn) is the largest fully coupled radiation hydrodynamics simulation of the reionization of the local Universe to date. It was performed using RAMSES-CUDATON running on 8192 nodes (i.e. 8192 GPUs) on the titan supercomputer at Oak Ridge National Laboratory to simulate a 64 h-1Mpc side box down to z=4.23. In this simulation, reionization proceeds self-consistently, driven by stellar radiation. We compare the simulation's reionization history, ionizing flux density, the cosmic star formation history and the CMB Thompson scattering optical depth with their observational values. Luminosity functions are also in rather good agreement with high redshift observations, although very bright objects (MAB1600 < -21) are overabundant in CoDa. We investigate the evolution of the intergalactic medium, and find that gas filaments present a sheathed structure, with a hot envelope surrounding a cooler core. They are however not able to self-shield, while regions denser than 10^-4.5 H atoms per comoving h^-3cm^3 are. Haloes below M ˜ 3.10^9 M⊙ are severely affected by the expanding, rising UV background: their ISM is quickly photo-heated to temperatures above our star formation threshold and therefore stop forming stars after local reionization has occured. Overall, the haloes between 10^(10-11) M⊙ dominate the star formation budget of the box for most of the Epoch of Reionization. Several additional studies will follow, looking for instance at environmental effects on galaxy properties, and the regimes of accretion.

Northwestern Namibia, at the landfall of the Walvis Ridge, was affected by the Tristan da Cunha mantle plume during continental rupture between Africa and South America, as evidenced by the presence of the Etendeka continental flood basalts. Here we use data from a passive-source seismological network to investigate the upper mantle structure and to elucidate the Cretaceous mantle plume-lithosphere interaction. Receiver functions reveal an interface associated with a negative velocity contrast within the lithosphere at an average depth of 80 km. We interpret this interface as the relic of the lithosphere-asthenosphere boundary (LAB) formed during the Mesozoic by interaction of the Tristan da Cunha plume head with the pre-existing lithosphere. The velocity contrast might be explained by stagnated and "frozen" melts beneath an intensively depleted and dehydrated peridotitic mantle. The present-day LAB is poorly visible with converted waves, indicating a gradual impedance contrast. Beneath much of the study area, converted phases of the 410 and 660 km mantle transition zone discontinuities arrive 1.5 s earlier than in the landward plume-unaffected continental interior, suggesting high velocities in the upper mantle caused by a thick lithosphere. This indicates that after lithospheric thinning during continental breakup, the lithosphere has increased in thickness during the last 132 Myr. Thermal cooling of the continental lithosphere alone cannot produce the lithospheric thickness required here. We propose that the remnant plume material, which has a higher seismic velocity than the ambient mantle due to melt depletion and dehydration, significantly contributed to the thickening of the mantle lithosphere.

What's known on the subject? and What does the study add? Numerous urological procedures can now be performed with robotic assistance. Though not definitely proven to be superior to conventional laparoscopy or traditional open surgery in the setting of a randomised trial, in experienced centres robot-assisted surgery allows for excellent surgical outcomes and is a valuable tool to augment modern surgical practice. Our review highlights the depth of history that underpins the robotic surgical platform we utilise today, whilst also detailing the current place of robot-assisted surgery in urology in 2011. The evolution of robots in general and as platforms to augment surgical practice is an intriguing story that spans cultures, continents and centuries. A timeline from Yan Shi (1023-957 bc), Archytas of Tarentum (400 bc), Aristotle (322 bc), Heron of Alexandria (10-70 ad), Leonardo da Vinci (1495), the Industrial Revolution (1790), 'telepresence' (1950) and to the da Vinci(®) Surgical System (1999), shows the incredible depth of history and development that underpins the modern surgical robot we use to treat our patients. Robot-assisted surgery is now well-established in Urology and although not currently regarded as a 'gold standard' approach for any urological procedure, it is being increasingly used for index operations of the prostate, kidney and bladder. We perceive that robotic evolution will continue infinitely, securing the place of robots in the history of Urological surgery. Herein, we detail the history of robots in general, in surgery and in Urology, highlighting the current place of robot-assisted surgery in radical prostatectomy, partial nephrectomy, pyeloplasty and radical cystectomy.

Isolated islets are important tools in diabetes research and are used for islet transplantation as a treatment for type 1 diabetes. Yet these cell clusters have a dramatic diffusion barrier that leads to core cell death. Computer modeling has provided theoretical size limitations, but little has been done to measure the actual rate of diffusion in islets. The purpose of this study was to directly measure the diffusion barrier in intact human islets and determine its role in restricting insulin secretion. Impeded diffusion into islets was monitored with fluorescent dextran beads. Dextran beads of 10-70 kDa failed to diffuse into the core of the intact islets, while 0.9 kDa probe was observed within the core of smaller islets. Diffusion of the fluorescent form of glucose, 2-NBDG, had similar diffusion limitations as the beads, with an average intra-islet diffusion rate of 1.5 ± 0.2 μm/min. The poor diffusion properties were associated with core cell death from necrosis, not apoptosis. Short-term exposure to a mild papain/0 Ca(2+) cocktail, dramatically reduced the diffusion barrier so that all cells within islets were exposed to media components. Lowering the diffusion barrier increased the immediate and long-term viability of islet cells, and tended to increase the amount of insulin released, especially in low glucose conditions. However, it failed to improve the large islet's glucose-stimulated insulin secretion. Thus, the islet diffusion barrier leads to low viability and poor survival of large islets, but is not solely responsible for the reduced insulin secretion of large isolated islets.

Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures.

Cathepsin L [EC 3.4.22.15] is secreted via lysosomal exocytosis by several types of cancer cells, including prostate and breast cancer cells. We previously reported that human cultured fibrosarcoma (HT 1080) cells secrete cathepsin L into the medium; this secreted cathepsin is 10-times more active than intracellular cathepsin. This increased activity was attributed to the presence of a 32-kDa cathepsin L in the medium. The aim of this study was to examine how this active 32-kDa cathepsin L is secreted into the medium. To this end, we compared the secreted active 32-kDa cathepsin L with lysosomal cathepsin L by using a novel gelatin zymography technique that employs leupeptin. We also examined the glycosylation and phosphorylation status of the proteins by using the enzymes endoglycosidase H [EC 3.2.1.96] and alkaline phosphatase [EC 3.1.3.1]. Strong active bands corresponding to the 32-kDa and 34-kDa cathepsin L forms were detected in the medium and lysosomes, respectively. The cell extract exhibited strong active bands for both forms. Moreover, both forms were adsorbed onto a concanavalin A-agarose column. The core protein domain of both forms had the same molecular mass of 30 kDa. The 32-kDa cathepsin L was phosphorylated, while the 34-kDa lysosomal form was dephosphorylated, perhaps because of the lysosomal marker enzyme, acid phosphatase. These results suggest that the active 32-kDa form does not enter the lysosomes. In conclusion, our results indicate that the active 32-kDa cathepsin L is secreted directly from the HT 1080 cells and not via lysosomal exocytosis. PMID:26674348

Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress.

In order to define the protease domain of human immunodeficiency virus 1, various regions of the pol open reading frame were cloned and expressed in Escherichia coli. Antiserum directed against the conserved retroviral protease active site was used to identify pol precursor and processed species containing the presumed protease domain. The smallest product that accumulates is about 11 kDa as measured by NaDodSO4/PAGE. This size agrees with that predicted from the presence in this region of two Phe-Pro sequences, which is one of the cleavage sites recognized by HIV protease. DNA encoding only the predicted 11-kDa protein was cloned, bypassing the need for autoprocessing, and the protein was expressed to a high level in E. coli. This form is active as demonstrated by its ability to specifically cleave protease-deficient pol protein in vivo in E. coli. Extracts of E. coli containing the 11-kDa protease also process human immunodeficiency virus gag substrates in vitro. These results demonstrate that the 11-kDa protease is sufficient for enzymatic activity and are consistent with a major role for this form in virus maturation. Images PMID:3282230

Hsp70 molecular chaperones contain three distinct structural domains, a 44 kDa N-terminal ATPase domain, a 17 kDa peptide-binding domain, and a 10 kDa C-terminal domain. The ATPase and peptide binding domains are conserved in sequence and are functionally well characterized. The function of the 10 kDa variable C-terminal domain is less well understood. We have characterized the secondary structure and dynamics of the C-terminal domain from the Escherichia coli Hsp70, DnaK, in solution by high-resolution NMR. The domain was shown to be comprised of a rigid structure consisting of four helices and a flexible C-terminal subdomain of approximately 33 amino acids. The mobility of the flexible region is maintained in the context of the full-length protein and does not appear to be modulated by the nucleotide state. The flexibility of this region appears to be a conserved feature of Hsp70 architecture and may have important functional implications. We also developed a method to analyze 15N nuclear spin relaxation data, which allows us to extract amide bond vector directions relative to a unique diffusion axis. The extracted angles and rotational correlation times indicate that the helices form an elongated, bundle-like structure in solution. PMID:10048327

Boiled silkworm pupa is a traditional food in Asia, and patients with silkworm pupa food allergy are common in these regions. Still now only one allergen from silkworm, arginine kinase, has been identified. The purpose of this study was to identify novel food allergens in silkworm pupa by analyzing a protein extract after heat treatment. Heat treated extracts were examined by proteomic analysis. A 27-kDa glycoprotein was identified, expressed in Escherichia coli, and purified. IgE reactivity of the recombinant protein was investigated by ELISA. High molecular weight proteins (above 100 kDa) elicited increased IgE binding after heat treatment compared to that before heat treatment. The molecular identities of these proteins, however, could not be determined. IgE reactivity toward a 27-kDa glycoprotein was also increased after heating the protein extract. The recombinant protein was recognized by IgE antibodies from allergic subjects (33.3%). Glycation or aggregation of protein by heating may create new IgE binding epitopes. Heat stable allergens are shown to be important in silkworm allergy. Sensitization to the 27-kDa glycoprotein from silkworm may contribute to elevation of IgE to silkworm.

... 32 National Defense 3 2014-07-01 2014-07-01 false Certificate for Signature by an Alternate (DA Form 4881-1-R) D Appendix D to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY SUPPLIES AND EQUIPMENT LOAN OF ARMY MATERIEL Pt. 623, App. D Appendix D to Part...

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Glycoproteins from the total vesicular fluid of Taenia crassiceps (VF-Tc) were prepared using three different purification methods, consisting of ConA-lectin affinity chromatography (ConA-Tc), preparative electrophoresis (SDS-PAGE) (14 gp-Tc), and monoclonal antibody immunoaffinity chromatography (18/14-Tc). The complex composition represented by the VF-Tc and ConA-Tc antigens revealed peptides ranging from 101- to 14-kDa and from 92- to 12-kDa, respectively. Immunoblotting using lectins confirmed glucose/mannose (glc/man) residues in the 18- and 14-kDa peptides, which are considered specific and immunodominant for the diagnosis of cysticercosis, and indicated that these fractions are glycoproteins. Serum antibodies from a patient with neurocysticercosis that reacted to the 14 gp band from T. crassiceps (Tc) were eluted from immunoblotting membranes and showed reactivity to 14 gp from Taenia solium. In order to determine the similar peptide sequence, the N-terminal amino acid was determined and analyzed with sequences available in public databases. This sequence revealed partial homology between T. crassiceps and T. solium peptides. In addition, mass spectrometry along with theoretical M(r) and pI of the 14 gp-Tc point suggested a close relationship to some peptides of a 150-kDa protein complex of the T. solium previously described. The identification of these common immunogenic sites will contribute to future efforts to develop recombinant antigens and synthetic peptides for immunological assays.

Dynamic Assessment (DA) derives from Vygotsky's (1987) insight that the use of mediation, attuned to learner needs, enables learners to perform beyond their current level of functioning, thereby providing insights into emerging capabilities. The instructional quality of mediation means that this process simultaneously creates possibilities for…

Two recently synthesized oxazolidinones: (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (DA-7157) and its corresponding pro-drug (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl disodium phosphate (DA-7218), have shown very good activity against several Gram positive bacteria, including Nocardia and Mycobacterium. In the present work we evaluated the therapeutic in vivo effects of DA-7218 on Nocardia brasiliensis. We first determined the plasma concentration of the prodrug in BALB/c mice using several doses and then tested its activity in an in vivo experimental actinomycetoma murine model. At the end of treatment, there was a statistically significant difference between the three drug receiving groups (25, 12.5 and 5 mg/kg) and the control group(saline solution) (p=0.001), proving that DA-7218 is effective for the treatment of experimental murine actinomycetoma. This compound could be a potential option for patients affected with mycetoma by Nocardia brasiliensis.

We report a pH-dependent conformational transition in short, defined homopolymeric deoxyadenosines (dA15) from a single helical structure with stacked nucleobases at neutral pH to a double-helical, parallel-stranded duplex held together by AH+-H+A base pairs at acidic pH. Using native PAGE, 2D NMR, circular dichroism (CD) and fluorescence spectroscopy, we have characterized the two different pH dependent forms of dA15. The pH-triggered transition between the two defined helical forms of dA15 is characterized by CD and fluorescence. The kinetics of this conformational switch is found to occur on a millisecond time scale. This robust, highly reversible, pH-induced transition between the two well-defined structured states of dA15 represents a new molecular building block for the construction of quick-response, pH-switchable architectures in structural DNA nanotechnology. PMID:19279188

The active volcanic island Tristan da Cunha, located at the southwestern and youngest end of the Walvis Ridge - Tristan/Gough hotspot track, is believed to be the surface expression of a huge thermal mantle anomaly. While several criteria for the diagnosis of a classical hotspot track are met, the Tristan region also shows some peculiarities. Consequently, it is vigorously debated if the active volcanism in this region is the expression of a deep mantle plume, or if it is caused by shallow plate tectonics and the interaction with the nearby Mid-Atlantic Ridge. Because of a lack of geophysical data in the study area, no model or assumption has been completely confirmed. We present the first amphibian P-wave finite-frequency travel time tomography of the Tristan da Cunha region, based on cross-correlated travel time residuals of teleseismic earthquakes recorded by 24 ocean-bottom seismometers. The data can be used to image a low velocity structure southwest of the island. The feature is cylindrical with a radius of ∼100 km down to a depth of 250 km. We relate this structure to the origin of Tristan da Cunha and name it the Tristan conduit. Below 250 km the low velocity structure ramifies into narrow veins, each with a radius of ∼50 km. Furthermore, we imaged a linkage between young seamounts southeast of Tristan da Cunha and the Tristan conduit.

The exposure of gastric mucosa to ethanol produces pathological changes such as inflammatory process, hemorrhagic erosions, even acute ulcers. The gastric mucosal lesions accompanied by a significant decrease of gastric blood flow and increase of reactive oxygen species (ROS) implicate a role of xanthine oxidase in ethanol-induced gastric hemorrhagic erosions. DA-9601, a novel antipeptic formulation of extracts of Artemisia asiatica Nakai, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intubation of absolute ethanol (4 g/kg) significantly induced gastrohemorrhagic lesions and lipid peroxidation in the rat stomach. Oral administration of DA-9601 at 40 mg/kg body weight significantly reduced ethanol-induced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of DA-9601 on alcohol-induced xanthine oxidase-type conversion and enzyme activity. The results suggest that alcohol-induced gastric mucosal damage may be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and that the preventive effect of DA-9601 on gastrohemorrhagic lesions would result from its inhibitory action against xanthine oxidase and oxidative stress in alcohol-treated rats.

An interdisciplinary partnership within an European Leonardo da Vinci project has developed a new approach aimed at educating secondary school students in the creation of built environments accessible to disabled people and at sensitizing them towards the inclusion of people with disabilities in all realms of social life. The AWARD (Accessible…

An e-mail survey and interviews collected data on use of information and communications technology (ICT) in Finnish Leonardo da Vinci mobility projects from 2000-02. Findings showed that the most common ICT tools used were e-mail, digital tools, and the World Wide Web; ICT was used during all project phases; the most common problems concerned…

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This paper aims to present the results of an investigation regarding the professional development of teachers who worked in the early years of basic education. The qualitative research involved teachers who participated in the "Observatório da Educação" project (MEC/CAPES). Because of the data amount, we choose to present the data…

Many AM&FM broadcasting stations in Japan are connected by the leased circuit system of NTT. Small delay and high performance AD/DA converter was developed for the system. The system was designed based on ITU-T J.41 Recommendation (384kbps), the transmission signal is 11bit-32 kHz where the Gain-frequency characteristics between 40Hz to 15kHz have to be quite flat. The ΔΣAD/DA converter LSIs for audio application in the market today realize very high performance. However the performance is not enough for the leased circuit system. We found that it is not possible to meet the delay and Gain-frequency requirements only by using ΔΣAD/DA converter LSI in normal operation, because 15kHz the highest frequency and 16kHz Nyquist frequency are too close, therefore there are aliasing around Nyquist frequency. In this paper, we designed AD/DA architecture having small delay (1msec) and sharp cut off LPF (100dB attenuation at 16kHz, and 1500dB/Oct from 15kHz to 16kHz) by operating ΔΣAD/DA converter LSIs over-sampling rate such as 128kHz and by adding custom LPF designed Infinite Impulse Response (IIR) filter. The IIR filter is a 16th order elliptic type and it is consist of eight biquad filters in series. We described how to evaluate the stability of IIR filter theoretically by calculating frequency response, Pole and Zero Layout and impulse response of each biquad filter, and experimentally by adding overflow detection circuit on each filters and input overlord signal.

The aims of this study were to compare the perioperative outcomes of da Vinci Xi to Si during robotic-assisted partial nephrectomy (RAPN) and to discuss the feasibility of our novel port placement scheme for the da Vinci Xi platform, to overcome the existing kinetic and technical difficulties we faced with the linear port placement in patients with a small body habitus. A retrospective data analysis of patients who underwent RPN using da Vinci Xi (n = 18) was carried out. The outcomes of the Xi group were compared with the Si group (n = 18) selected using a case-matched methodology. For da Vinci Xi, we applied the universal linear port placement in 12 patients and our modified port placement in the remaining 6 patients. The Xi group had a shorter mean docking time of 17.8 ± 2.6 min compared to the Si group of 20.5 ± 2.1 min (p = 0.002); otherwise, no significant difference was present with regard to the remaining perioperative variables (p > 0.05). The modified Xi port placement had a shorter mean console time of 70.8 ± 9.7 min compared to the universal linear port placement of 89.3 ± 17.2 min (p = 0.03). Moreover, it provided a broader field of vision with excellent robotic arms movement, minimizing collisions and allowing an easier and comfortable surgical assist. Da Vinci Xi appears to be feasible and safe during RPN with similar outcomes to Si. The novel Xi port placement makes surgery easier in patients with low BMI.

The maize opaque2 (o2) mutant has a high nutritional value but it develops a chalky endosperm that limits its practical use. Genetic selection for o2 modifiers can convert the normally chalky endosperm of the mutant into a hard, vitreous phenotype, yielding what is known as quality protein maize (QPM). Previous studies have shown that enhanced expression of 27-kDa γ-zein in QPM is essential for endosperm modification. Taking advantage of genome-wide association study analysis of a natural population, linkage mapping analysis of a recombinant inbred line population, and map-based cloning, we identified a quantitative trait locus (qγ27) affecting expression of 27-kDa γ-zein. qγ27 was mapped to the same region as the major o2 modifier (o2 modifier1) on chromosome 7 near the 27-kDa γ-zein locus. qγ27 resulted from a 15.26-kb duplication at the 27-kDa γ-zein locus, which increases the level of gene expression. This duplication occurred before maize domestication; however, the gene structure of qγ27 appears to be unstable and the DNA rearrangement frequently occurs at this locus. Because enhanced expression of 27-kDa γ-zein is critical for endosperm modification in QPM, qγ27 is expected to be under artificial selection. This discovery provides a useful molecular marker that can be used to accelerate QPM breeding. PMID:27092004

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects. PMID:21860559

DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

The effects of growth-promoting hormone diethyl aminoethyl hexanoate (DA-6) and EDTA, either alone or in combination applied to original soil or lead (Pb) spiked soil on Pb phytoextraction, subcellular distribution and chemical forms in Lolium perenne were studied. EDTA addition alone significantly reduced plant biomass though it increased Pb accumulation (P<0.05). Foliar spray of DA-6 alone increased both plant biomass and Pb accumulation (P<0.05), with 10μM DA-6 being the most effective. DA-6 combined with EDTA compensated the adverse effect of the latter on plant growth, and resulted in a synergistic effect on Pb uptake and translocation, with the maximum accumulation occurring in the EDTA+10μM DA-6 treatment. At the subcellular level, about 35-66% of Pb was distributed in cell wall and 21-42% in soluble fraction, with a minority present in cellular organelles fraction. EDTA addition alone increased the proportion of Pb in soluble and cellular organelles fraction, while DA-6 detoxified Pb in plant by storing additional Pb in cell wall, and 10μM DA-6 was the most effective. Of the total Pb in plant shoot, 27-52% was NaCl extractable, 22-47% HAc extractable, followed by other fractions. Contrary to EDTA, DA-6 significantly decreased Pb migration in plant. These results suggest that Pb fixation by pectates and proteins in cell wall and compartmentalization by vacuole might be responsible for Pb detoxification in plant, and the combined use of EDTA and 10μM DA-6 appears to be optimal for improving the remediation efficiency of L. perenne for Pb contaminated soil.

Nerve growth factor (NGF)-induced neuronal regeneration has emerged as a strategy to treat neuronal degeneration-associated disorders. However, direct NGF administration is limited by the occurrence of adverse effects at high doses of NGF. Therefore, development of a therapeutic strategy to promote the NGF trophic effect is required. In view of the lack of understanding of the mechanism for potentiating the NGF effect, this study investigated molecular targets of DA-9801, a well-standardized Dioscorea rhizome extract, which has a promoting effect on NGF. An increase in intracellular calcium ion level was induced by DA-9801, and chelation of extracellular calcium ions with ethylene-bis(oxyethylenenitrilo)tetraacetic acid (EGTA) suppressed the potentiating effect of DA-9801 on NGF-induced neurite outgrowth. In addition, EGTA treatment reduced the DA-9801-induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), the major mediators of neurite outgrowth. To find which calcium ion-permeable channel contributes to the calcium ion influx induced by DA-9801, we treated PC12 cells with various inhibitors of calcium ion-permeable channels. NF449, a P2X1 receptor selective antagonist, significantly abolished the potentiating effect of DA-9801 on NGF-induced neurite outgrowth and abrogated the DA-9801-induced ERK1/2 phosphorylation. In addition, transfection with siRNA of P2X1 receptor significantly reduced the DA-9801-enhanced neurite outgrowth. In conclusion, calcium ion influx through P2X1 receptor mediated the promoting effect of DA-9801 on NGF-induced neurite outgrowth via ERK1/2 phosphorylation.

The relationship between Bacillus thuringiensis Cry1Aa, Cry1Ab and Cry1Ac delta-endotoxin binding and pore formation was investigated using a purified 170 kDa aminopeptidase N (APN) from Heliothis virescens brush border membranes. Aminopeptidases with molecular sizes of 110, 140 and 170 kDa were eluted from a Cry1Ac toxin affinity column using N-acetylgalactosamine. The 140 kDa aminopeptidase has a cross-reacting determinant typical of a cleaved glycosyl-phosphatidylinositol anchor. After mild base treatment to de-acylate the glycosyl-phosphatidylinositol linkage and incubation in phosphatidyl inositol phospholipase C, anti-cross-reacting determinant antibody recognized the 170 kDa protein. Kinetic binding characteristics of Cry1A toxins to purified 170 kDa APN were determined using surface plasmon resonance. Cry1Aa, Cry1Ab and Cry1Ac, but not Cry1C and Cry1E toxins recognized 170 kDa APN. Each Cry1A toxin recognized two binding sites: a high affinity site with KD ranging from 41 to 95 nM and a lower affinity site with KD in the 325 to 623 nM range. N-acetylgalactosamine inhibited Cry1Ac but not Cry1Aa and Cry1Ab binding to 170 kDa APN. When reconstituted into phospholipid vesicles, the 170 kDa APN promoted toxin-induced 86Rb+ release for Cry1A toxins, but not Cry1C toxin. Furthermore Cry1Ac, the Cry protein most toxic to H. virescens larvae, caused 86Rb+ release at lower concentrations, and to a greater extent than Cry1Aa and Cry1Ab toxins. The correlation between toxin-binding specificity and 86Rb+ release strongly suggests that the purified 170 kDa APN is the functional receptor A in the H. virescens midgut epithelial cell brush border membranes.

Background/Aims The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Western countries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. Methods In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among 3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. The primary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. Results The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptom improvement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups. Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes and dyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. Conclusions DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacy of DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 and pantoprazole in patients with FD. PMID:26811504

Mammalian fertilization is accomplished by the interaction between sperm and egg. Previous studies from this laboratory have identified a stable acrosomal matrix assembly from the bovine sperm acrosome termed the outer acrosomal membrane-matrix complex (OMC). This stable matrix assembly exhibits precise binding activity for acrosin and N-acetylglucosaminidase. A highly purified OMC fraction comprises three major (54, 50, and 45 kDa) and several minor (38-19 kDa) polypeptides. The set of minor polypeptides (38-19 kDa) termed "OMCrpf polypeptides" is selectively solubilized by high-pH extraction (pH 10.5), while the three major polypeptides (55, 50, and 45 kDa) remain insoluble. Proteomic identification of the OMC32 polypeptide (32 kDa polypeptide isolated from high-pH soluble fraction of OMC) yielded two peptides that matched the NCBI database sequence of acrosin-binding protein. Anti-OMC32 recognized an antigenically related family of polypeptides (OMCrpf polypeptides) in the 38-19-kDa range with isoelectric points ranging between 4.0 and 5.1. Other than glycohydrolases, OMC32 may also be complexed to other acrosomal proteins. The present study was undertaken to identify and localize the OMC32 binding polypeptides and to elucidate the potential role of the acrosomal protein complex in sperm function. OMC32 affinity chromatography of a detergent-soluble fraction of bovine cauda sperm acrosome followed by mass spectrometry-based identification of bound proteins identified acrosin, lactadherin, SPACA3, and IZUMO1. Co-immunoprecipitation analysis also demonstrated the interaction of OMC32 with acrosin, lactadherin, SPACA3, and IZUMO1. Our immunofluorescence studies revealed the presence of SPACA3 and lactadherin over the apical segment, whereas IZUMO1 is localized over the equatorial segment of Triton X-100 permeabilized cauda sperm. Immunoblot analysis showed that a significant portion of SPACA3 was released after the lysophosphatidylcholine (LPC)-induced acrosome

Mammalian fertilization is accomplished by the interaction between sperm and egg. Previous studies from this laboratory have identified a stable acrosomal matrix assembly from the bovine sperm acrosome termed the outer acrosomal membrane-matrix complex (OMC). This stable matrix assembly exhibits precise binding activity for acrosin and N-acetylglucosaminidase. A highly purified OMC fraction is comprised of three major (54, 50, and 45kDa) and several minor (38–19kDa) polypeptides. The set of minor polypeptides (38–19kDa) termed “OMCrpf polypeptides” is selectively solubilized by high-pH extraction (pH 10.5) while the three major polypeptides (55, 50 and 45kDa) remain insoluble. Proteomic identification of the OMC32 polypeptide (32kDa polypeptide isolated from high-pH soluble fraction of OMC) yielded two peptides that matched the NCBI database sequence of acrosin-binding protein. Anti-OMC32 recognized an antigenically related family of polypeptides (OMCrpf polypeptides) in the 38–19kDa range with isoelectric points ranging between 4.0 and 5.1. Other than glycohydrolases, OMC32 may also be complexed to other acrosomal proteins. The present study was undertaken to identify and localize the OMC32 binding polypeptides and to elucidate the potential role of the acrosomal protein complex in sperm function. OMC32 affinity chromatography of a detergent soluble fraction of bovine cauda sperm acrosome followed by mass spectrometry-based identification of bound proteins identified acrosin, lactadherin, SPACA3, and IZUMO1. Co-immunoprecipitation analysis also demonstrated the interaction of OMC32 with acrosin, lactadherin, SPACA3, and IZUMO1. Our immunofluorescence studies revealed the presence of SPACA3 and lactadherin over the apical segment; whereas, IZUMO1 is localized over the equatorial segment of Triton X-100 permeabilized cauda sperm. Immunoblot analysis showed that a significant portion of SPACA3 was released after the lysophosphatidyl choline (LPC

This work deals with the genesis and paleoenvironmental significance of relict slope deposits in Serra da Estrela, Central Portugal and is part of a wider sedimentological and dating approach. The aim is to identify what microstructures indicate frost weathering, witch mechanisms are responsible for their development and the effectiveness of frost weathering across an altitudinal profile. Our goals are to contribute to the better understanding of the morphogenetical significance of the different types of slope deposits, clarifying the role of cold environment processes and develop a chronological framework for the Late Quaternary evolution of the slope environment of the mountains of Western Iberia. Quartz grains, 0.5 mm in diameter, were collected from samples from stratified, head and debris-flow deposits. Cailleux (1942) analysis, with modifications from Gozdzik (1980), was performed allowing assessing frosting and rounding, as well as the effects of later frost weathering in vertical profiles from slope deposits. Grains were also analysed using a scanning electron microscope (SEM) following Mahaney (2002). The effects of frost weathering comprise several microstructures such as breakage blocks, conchoidal fractures and fresh surfaces. Breakage blocks microstructures are the most common. Two types of frost weathering were distinguished: weathering of the P type is mainly initiated on convex fragments of grains as the result of ice segregation, and F type is linked to the volumetric expansion of ice and usually observed within concave linear microstructures. The frost action index (FAI) was estimated from the rate of microstructures from frost weathering. FAI varies between 0 and 3. The values of the sediments from the slope deposits vary between 1.2 and 2.05. This approach was for the first time applied on slope deposits from Serra da Estrela. There is a clear correlation between deposits in weathering type. Samples that display intensive physical weathering in

The human being has always been concerned with the preservation of memory, of cultural heritage. Only now he started to protect its natural heritage and the immediate environment. It is time to learn how to protect the Earth's past and, through this protection and learn to know it. This memory comes before the human memory. It is a new asset: the geological heritage, a book written long before our appearance on the Planet (...)"(IPHAN, 2014). Since the XXth century, Brazilian geographers (GUERRA, 1980; AB'SABER, 2003 and others) dedicated to carry out research on the relationship of geographical knowledge between the environment and society. On the other hand, Brazil is a signatory of the Convention for the Protection of the World Heritage Cultural and Natural (UNESCO, 1972), where the nations recognize to keep under their responsibility the conservation, to the rest of humanity and future generations, goods of exceptional value situated within its territorial limits, considered as World Heritage. Under this perspective, it is proposed here a survey on the environmental impacts, resulting from the human activities that directly or indirectly affect the health, safety and welfare of the population; social and economic activities; the biota; the aesthetic and sanitary conditions of the environment; the quality of the environment (CONAMA Resolution 001/86) - and resulting geotourism practiced on trails - paths for pedestrians, cyclists and animals, existing in the protected area of the Serra da Bocaina National Park, in Rio de Janeiro State, such as unplanned use, erosive features, presence of litter, graffiti and burned, degraded areas on the trails indicating the need for recovery (drainage, etc.). This survey is based on research work of the environmental degradation and analysis undertaken by the Laboratory of Environmental Geomorphology and Soils Degradation (LAGESOLOS / UFRJ) in the area, in order to contribute to the geoconservation, so that the encountered

Background: The role of vitamin D in the pathogenesis of rheumatoid arthritis is under investigation. This study was designed to evaluate the correlation between serum values of 25(OH) vitamin D [25(OH)D] and disease activity in rheumatoid arthritis (RA) patients according to Disease Activity Score 28 joints and ESR (DA S28 ESR). Methods: Ninety-nine patients according to ACR classification criteria for RA and 68 healthy controls were included in this study. The participants with known confounding risk factors affecting serum values of 25(OH)D were excluded. All patients were under treatment with supplementary calcium carbonate (1500mg), 25(OH)D (800U), and Hydroxychloroquine (6mg/kg). The control group was mostly recruited from patients’ relatives who lived with them to minimize the impact of diverse lifestyles on 25(OH)D status. Disease activity was assessed by DA S28 ESR. Serum concentrations of 25(OH)D were measured. Serum values of 25(OH)D less than 50 nmol/L were considered 25(OH)D deficiency. Results: The mean 25(OH)D serum values were 83.74±46.45 nmol/L in patients and 46.53±34.07 nmol/L in controls. After adjustment for age, sex and BMI, multivariate analysis showed no correlation between 25(OH)D serum levels and DAS in RA (P=0.29, rp=0.11). However, 25(OH)D serum values were significantly lower in patients with early diagnosed RA compared with the other patients (p=0.012). In the early diagnosed patients, 25(OH)D and anti-CCP serum values were negatively correlated (P=0.04, rs=-0.5). Conclusion: This study showed that there was no correlation between 25(OH)D serum values and DAS over a short duration of disease course. However, in early RA, 25(OH) D serum values were lower than the established RA. PMID:25202442

Interaction of plasma membrane with the cytoskeleton involves a large number of proteins, among them a 36 kDa protein that was found to be involved in the interaction with actin filaments. We have isolated a 36 kDa protein from bovine aorta as a monomer and in a complex with a 10 kDa protein. Partial amino acid sequence determinations show that the 36 kDa and 10 kDa proteins isolated from bovine aorta are analogous to or identical with corresponding proteins purified from bovine intestine already described by Kristensen, Saris, Hunter, Hicks, Noonan, Glenney & Tack [(1986) Biochemistry 25, 4497-4503]. We report here that the association of the 10 kDa protein with the 36 kDa protein confers specific calmodulin-binding and actin-severing properties on the complex that are not possessed by the 36 kDa monomer alone. These findings suggest that the protein complex could be involved in thin-filament-related structures or could modulate some Ca2+-regulated events mediated by calmodulin. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 7. PMID:2970844

This study was designed to investigate dopaminergic mechanisms in human vasculature using the selective vascular dopamine receptor agonist fenoldopam in vivo and in vitro. In vivo, forearm blood flow was measured plethysmographically and in vitro isolated rings of human blood vessels from a variety of sites were used for tissue bath studies. Intra-arterial fenoldopam markedly increased forearm blood flow, this effect was antagonised by (R) sulpiride, a vascular dopamine (DA1) antagonist, but not by metoclopramide, a neuronal (DA2) antagonist, or by guanethidine, an adrenergic neurone blocking agent. In vitro, fenoldopam relaxed preconstricted human renal, mesenteric and lumbar arteries, but not saphenous vein in a concentration dependent manner. (RS) sulpiride and SCH 23390 competitively antagonised this effect. These studies demonstrate the presence of a vasodilatory vascular dopamine receptor in man both in vivo and in vitro. PMID:2878679

The experience of using the dynamic atlas of the experimental data and mathematical models of their description in the problems of adjusting parametric models of observable values depending on kinematic variables is presented. The functional possibilities of an image of a large number of experimental data and the models describing them are shown by examples of data and models of observable values determined by the amplitudes of elastic scattering of hadrons. The Internet implementation of an interactive tool DaMoScope and its interface with the experimental data and codes of adjusted parametric models with the parameters of the best description of data are schematically shown. The DaMoScope codes are freely available.

Beginning from the XV century, mechanical materialism underwent an evolution in "biological mechanics" within the scientific doctrine. Among the greatest exponents of this new current there were two Italian men, Leonardo da Vinci (1452-1519) and Girolamo da Acquapendente (1533-1619). By the trend given by Leonardo, the myology, instead of being a static science, took a dynamic meaning and valence. Later, Fabrizi resumed and investigated the subject above all in its less known expression, elaborating an original theory. With Acquapendente, the anatomy lost its merely descriptive pecularity and evolved in analysis of the structure in connection with the function. Moreover, he opposed the syllogism against the mechanic language and the mathematical formulation. A new scientific way will be afterwards characterized by Galileo Galilei in the field of the physics and by Giovanni Alfonso Borrelli in the biology.

The experience of using the dynamic atlas of the experimental data and mathematical models of their description in the problems of adjusting parametric models of observable values depending on kinematic variables is presented. The functional possibilities of an image of a large number of experimental data and the models describing them are shown by examples of data and models of observable values determined by the amplitudes of elastic scattering of hadrons. The Internet implementation of an interactive tool DaMoScope and its interface with the experimental data and codes of adjusted parametric models with the parameters of the best description of data are schematically shown. The DaMoScope codes are freely available.

Autoantibodies from a patient with chronic rheumatoid arthritis recognized an antigen localized in the Golgi complex of various cells from different tissues and species. The autoantibodies were used as a probe for screening human QGP-1 cDNA library, resulting in identification of a 10.3-kb cDNA. The cDNA insert contained an open reading frame which encodes a 3225-residue protein with a calculated mass of 372 kDa. The predicted protein was found to have no NH2-terminal signal sequence but a single hydrophobic domain at the COOH terminus. These results indicate that the 372-kDa antigen is cytoplasmically disposed and anchored to the Golgi membrane by the COOH-terminal hydrophobic domain.

The radiative damping of acoustic and MHD waves that propagate through white dwarf photospheric layers is studied, and other damping processes that may be important for the propagation of the MHD waves are calculated. The amount of energy remaining after the damping processes have occurred in different types of waves is estimated. The results show that lower acoustic fluxes should be expected in layered DA and homogeneous DB white dwarfs than had previously been estimated. Acoustic emission manifests itself in an enhancement of the quadrupole term, but this term may become comparable to or even lower than the dipole term for cool white dwarfs. Energy carried by the acoustic waves is significantly dissipated in deep photospheric layers, mainly because of radiative damping. Acoustically heated corona cannot exist around DA and DB white dwarfs in a range T(eff) = 10,000-30,000 K and for log g = 7 and 8. However, relatively hot and massive white dwarfs could be exceptions.

The Brazilian Institute for the History of Medicine was founded on 1945 by the physician Ivolino de Vasconcellos. Because the movement intended to be of national scope, the Federação Nacional de História da Medicina e Ciências Afins was also created (National Federation for the History of Medicine and Related Sciences). The latter group had a humanistic understanding of medicine, wherein the history of medicine played a central role; since this subject honored great names and achievements in medicine, members of the federation felt it was a prime tool in the ethical and humanistic training of healthcare professionals. Thus was born the Revista Brasileira de História da Medicina, which fostered scientific and academic production and events in the field of history of medicine and also registered the Federation's activities and scientific output.

In this study, concentrations of several heavy metals (Cu, Pb, Zn, Ni, Cr, and Cd) were measured in Katelysia hiantina, Anomalocardia squamosa, Perna viridis, Anadara antiquata, Paphia undulata, and Sanguinolaria diphos bivalve mollusks from Da-Peng Bay Lagoon near the south-southwestern coast of Taiwan. The metal pollution index (MPI) values were highest and lowest in winter and autumn, respectively. The MPI value in the viscera of P. viridis was higher than in muscles. In all four seasons, Zn concentrations in viscera and muscles of P. viridis were higher than for other metals. The capacities of A. squamosa to accumulate the concentrations of Cu, Ni, and Cr and of A. antiquata to accumulate concentrations of Pb, Zn, and Cd were significant. Analytical results suggested that A. squamosa and A. antiquata may be used as bioindicators for monitoring Cu, Ni, Cr, Pb, Zn, and Cd heavy-metal pollution in Da-Peng Bay Lagoon throughout the year.

We follow the Chumbes-Holf da Silva-Hott mechanism to study the (quasi)localization of the U(1) gauge field on the Bloch brane. The localization and resonances of the U(1) gauge field are discussed for four kinds of Bloch brane solutions: the original and generalized Bloch brane solutions, as well as the degenerate Bloch brane solutions I and II. With the Chumbes-Holf da Silva-Hott mechanism, we find that the mass spectrum of the gauge field Kaluza-Klein modes is continuous and there is no tachyonic mode. The zero mode is localized on all the branes and there are resonant Kaluza-Klein modes on the degenerate Bloch branes.

We report the nucleotide sequence of a 2652 bp derived from a chicken 90-kDa heat shock protein (hsp 90) genomic clone. This fragment contains 890 bp of the 5' flanking region and 1762 bp of structural gene sequence encoding the first 85 amino acids of the protein. The start site of transcription was determined by primer extension and RNase mapping. Two introns have been identified. The first intron presents two features in common with the unique intron of the hsp 83 of drosophila: its location just before the ATG initiation codon and its length of approximately 1.3 Kb. The 5' flanking region contains a TATAA element, a CCAAT box and several putative cis-regulatory elements that might account for the basal level of expression and developmental regulation of the gene. Functional analyses show that hsp 90 gene expression is constitutive and heat inducible and that a full heat shock response requires the cooperativity of two distinct blocks of overlapping heat shock response elements. Images PMID:2762125

In 2006, after a visual inspection of the Leonardo da Vinci's Atlantic Codex by a scholar, active molds were reported to have been present on Codex pages showing areas of staining. In the present paper, molecular methods were used to assess the current microbiological risk to stained pages of the manuscript. Bacterial and fungal communities were sampled by a non-invasive technique employing nitrocellulose membranes. Denaturing gradient gel electrophoresis of 16 S rRNA gene and internal transcribed space regions were carried out to study the structure of the bacterial and fungal communities and band patterns were analyzed by the multivariate technique of principal component analysis. Any relationship between the presence of an active microbial community and staining was excluded. The presence of potential biodeteriogens was evaluated by constructing bacterial and fungal clone libraries, analyzing them by an operational taxonomic unit (OTU) approach. Among the bacteria, some OTUs were associated with species found on floors in clean room while others were identified with human skin contamination. Some fungal OTU representatives were potential biodeteriogens that, under proper thermo-hygrometric conditions, could grow. The retrieval of these potential biodeteriogens and microorganisms related to human skin suggests the need for a continuous and rigorous monitoring of the environmental conditions, and the need to improve handling procedures.

The construction of the Faraday Cup portion of the SWIE instrument on the Wind spacecraft, participation in Mission Operations, and Data Analysis (MO and DA) of observations of the solar wind has been supported by a sequence of grants. This 'final' Report represents work done on Mission Operations and Data Analysis for the Faraday Cup portion of the SWE. The work reported here was supported under NASA Grant NAG5-7359 (OSP 6701100) from June 1998 to October 2001. It should be noted that this work is continuing under NASA Grant NAG-10915, and therefore this report is 'final' only in the sense that the Grant has changed its number; a future report will cover the entire period of work. We have two types of obligations under these contracts: (1) To provide and assure the validity of "Key Parameters" which describe the basic properties of the solar wind on a daily basis. We have provided our 92 second observations daily via plots and parameters available from our Web site: http://web.mit.edu/space/www/wind/wind.html (2). To carry out scientific studies based on our observations. To document the extent of our research, we are including below a list of publications and presentations related to this project. The observations from Wind have made a major contribution to the study of the solar wind, and have every indication of continuing to do so.

A series of studies were undertaken to assess the effect of oral fenoldopam, a specific DA1 dopamine receptor agonist on blood pressure and renal function in patients with mild essential hypertension. Six patients with essential hypertension were entered into a dose-ranging study and received either placebo, 25, 50 or 100 mg fenoldopam. A significant, dose-related reduction in diastolic blood pressure, and increase in heart rate was demonstrated (both P less than 0.05), maximal at 45 min to 1 h. Fenoldopam increased plasma renin activity. In a double-blind study, seven patients received a single dose of fenoldopam 100 mg or placebo. Fenoldopam produced a significant fall in systolic (P less than 0.05) and diastolic (P less than 0.01) blood pressure and renal vascular resistance (P less than 0.01). Urine flow rate (P less than 0.05), sodium excretion (P less than 0.01), plasma renin activity (P less than 0.05) and plasma aldosterone (P less than 0.05) increased. Five patients underwent measurement of the above parameters following a single dose of fenoldopam 100 mg with a repeat of these measurements after they had taken fenoldopam 100 mg four times daily for 1 month. The acute response of blood pressure to the single dose appeared unchanged but tachyphylaxis was evident in the responses of heart rate, plasma renin activity and plasma aldosterone. PMID:2868748

An exhaustive study of the phenolic composition of almond ( Prunus dulcis (Mill.) D.A. Webb) skins was carried out in order to evaluate their potential application as a functional food ingredient. Using the HPLC-DAD/ESI-MS technique, a total of 33 compounds corresponding to flavanols, flavonols, dihydroflavonols and flavanones, and other nonflavonoid compounds were identified. Peaks corresponding to another 23 structure-related compounds were also detected. MALDI-TOF MS was applied to characterize almond skin proanthocyanidins, revealing the existence of a series of A- and B-type procyanidins and propelargonidins up to heptamers, and A- and B-type prodelphinidins up to hexamers. Flavanols and flavonol glycosides were the most abundant phenolic compounds in almond skins, representing up to 38-57% and 14-35% of the total quantified phenolics, respectively. Due to their antioxidant properties, measured as oxygen-radical absorbance capacity (ORAC) at 0.398-0.500 mmol Trolox/g, almond skins can be considered as a value-added byproduct for elaborating dietary antioxidant ingredients.

Observations are reported which refine the binary ephemeris of the Feige 24 system, which contains a peculiar hot DA white dwarf and an M dwarf with an atmosphere illuminated by extreme ultraviolet radiation from the white dwarf. With the new ephemeris and a set of IUE high-dispersion spectra, showing phase-dependent redshifted C IV, N V, and Si IV resonance lines, the orbital velocity, and hence the mass (0.54 + or {minus} 0.20 solar masses), and the gravitational redshift of the white dwarf (14.1 + or {minus} 5.2 km/s) are determined independently. It is shown that the measured Einstein redshift is consistent with an estimated radius for the white dwarf obtained from a model atmosphere solid angle and a parallax measurement. This radius is twice the Hamada-Salpeter radius for the given mass and offers a prospect to investigate the presence of a massive hydrogen envelope in that white dwarf star. 27 refs.

Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

Ginkgo biloba seeds are widely used as a food and traditional medicine in China. In the present study, a novel antioxidant protein named GBSP was purified from Ginkgo biloba seeds. The protein (GBSP) was purified by homogenization of Ginkgo biloba seed powder in saline solution, 70% ammonium sulphate precipitation, filtration on a DEAE-Cellulose52 anion exchange column, gel filtration on a Sephadex G-50 column, and preparative chromatography on a C(18) column using RP-HPLC. GBSP showed an apparent molecular weight of 18 kDa by SDS-PAGE and MALDI-TOF/MS analyses. The amino acid sequence obtained by MALDI-TOF/TOF MS analysis showed GBSP was a novel protein, as no matching protein in was found the database. The protein exhibited significant antioxidant activities against free radicals such as DPPH, ABTS and superoxide anion and showed higher activity than α-tocopherol in a linoleic acid emulsion assay system. Furthermore, GBSP exhibited notable reducing power and a strong chelating effect on Cu(2+) and Fe(2+). Therefore, the present study demonstrates, for the first time, that this novel protein from Ginkgo biloba seeds is an excellent antioxidant.

The Amazon tree Aniba rosaeodora Ducke (rosewood) provides an essential oil valuable for the perfume industry, but after decades of predatory extraction it is at risk of extinction. The extraction of the essential oil from wood implies the cutting of the tree, and then the study of oil extracted from the leaves is important as a sustainable alternative. The goal of this study was to test the applicability of Raman spectroscopy and Partial Least Square Discriminant Analysis (PLS-DA) as means to classify the essential oil extracted from different parties (wood, leaves and branches) of the Brazilian tree A. rosaeodora. For the development of classification models, the Raman spectra were split into two sets: training and test. The value of the limit that separates the classes was calculated based on the distribution of samples of training. This value was calculated in a manner that the classes are divided with a lower probability of incorrect classification for future estimates. The best model presented sensitivity and specificity of 100%, predictive accuracy and efficiency of 100%. These results give an overall vision of the behavior of the model, but do not give information about individual samples; in this case, the confidence interval for each sample of classification was also calculated using the resampling bootstrap technique. The methodology developed have the potential to be an alternative for standard procedures used for oil analysis and it can be employed as screening method, since it is fast, non-destructive and robust.

Few sites have been well sampled for bats, and samplings in islands are even scarcer. Therefore, the objectives of the present study were: (1) to list the bat species of Ilha da Marambaia; (2) to compare richness, abundance and biomass of bat guilds found there; (3) to analyse abundance patterns of bat species; and (4) to compare richness, abundance and composition of the bat fauna among different kinds of environment. To capture bats we used mist nets set in five different environments, totalising 3559.2 net-hours, during 37 nights between October 2006 and August 2008. A total of 1,133 captures were accomplished, comprising 34 species from five families. The most abundant species was Molossus molossus. Frugivorous bats exhibited higher richness, abundance and biomass if compared to other guilds. Most species (N = 22) exhibited abundances between 1 to 10% of all captures. Sixteen species were restricted to just one of the environments sampled. The high richness may be attributed to sampling carried out in several environments, and to the capture of insectivorous species over water bodies.

Trypanosoma cruzi genomic database was screened for hypothetical proteins that showed high probability of being secreted or membrane anchored and thus, likely involved in host-cell invasion. A sequence that codes for a 21kDa protein that showed high probability of being secreted was selected. After cloning this protein sequence, the results showed that it was a ubiquitous protein and secreted by extracellular amastigotes. The recombinant form (P21-His(6)) adhered to HeLa cells in a dose-dependent manner. Pretreatment of host cells with P21-His(6) inhibited cell invasion by extracellular amastigotes from G and CL strains. On the other hand, when the protein was added to host cells at the same time as amastigotes, an increase in cell invasion was observed. Host-cell pretreatment with P21-His(6) augmented invasion by metacyclic trypomastigotes. Moreover, polyclonal antibody anti-P21 inhibited invasion only by extracellular amastigotes and metacyclic trypomastigotes from G strain. These results suggested that P21 might be involved in T. cruzi cell invasion. We hypothesize that P21 could be secreted in the juxtaposition parasite-host cell and triggers signaling events yet unknown that lead to parasite internalization.

Arguably, the best method for determining the effective temperature (Teff) and surface gravity (log g) of a DA white dwarf is by fitting the Hydrogen Lyman and Balmer absorption features. However, as has been shown for white dwarfs with Teff>50,000K, the calculated value from the Lyman and Balmer lines are discrepant, which worsens with increasing temperature. Many different solutions have been suggested, ranging from the input physics used to calculate the models, to interstellar reddening. We will focus on the former, and consider three variables. The first is the atomic data used, namely the number of transitions included in line blanketing treatments and the photoionization cross sections. The second is the stark broadening treatment used to synthesise the Lyman and Balmer line profiles, namely the calculations performed by Lemke (1997) and Tremblay & Bergeron (2009). Finally, the third is the atmospheric content. The model grids are calculated with a pure H composition, and a metal polluted composition using the abundances of Preval et al. (2013). We present the preliminary results of our analysis, whereby we have determined the Teff for a small selection of white dwarfs. We plan to extend our analysis by allowing metallicity to vary in future model grids.

The third meeting organised by the European Federation of Biotechnology (EFB) on advances in Applied Synthetic Biotechnology in Europe (ASBE) was held in Costa da Caparica, Portugal, in February 2016. Abundant novel applications in synthetic biology were described in the six sessions of the meeting, which was divided into technology and tools for synthetic biology (I, II and III), bionanoscience, biosynthetic pathways and enzyme synthetic biology, and metabolic engineering and chemical manufacturing. The meeting presented numerous methods for the development of novel synthetic strains, synthetic biological tools and synthetic biology applications. With the aid of synthetic biology, production costs of chemicals, metabolites and food products are expected to decrease, by generating sustainable biochemical production of such resources. Also, such synthetic biological advances could be applied for medical purposes, as in pharmaceuticals and for biosensors. Recurrent, linked themes throughout the meeting were the shortage of resources, the world's transition into a bioeconomy, and how synthetic biology is helping tackle these issues through cutting-edge technologies. While there are still limitations in synthetic biology research, innovation is propelling the development of technology, the standardisation of synthetic biological tools and the use of suitable host organisms. These developments are laying a foundation to providing a future where cutting-edge research could generate potential solutions to society's pressing issues, thus incentivising a transition into a bioeconomy.

Four overlapping cDNA clones encoding a partial sequence of the cation-independent 215-kDa mannose 6-phosphate receptor have been identified by screening a fetal calf liver cDNA library with oligonucleotide probes. RNA hybridization analysis showed that the length of the mRNA is approximately 9.5 kilobases. Sequence analysis demonstrated that the clones consist of 4647 contiguous nucleotides and contain an open reading frame coding for a polypeptide of 1461 amino acids, which we estimate represents greater than 75% of the primary structure of the receptor. The deduced amino acid sequence indicates that the receptor has a carboxyl-terminal cytoplasmic domain of 163 amino acids that is rich in acidic residues, a 23-amino acid transmembrane segment, and an extracellular domain containing at least eight homologous repeats of approximately 145 amino acids. One of the repeats contains an additional 43-residue segment that is similar to the type II repeat of fibronectin. Each repeat contains a highly conserved 13-amino acid unit bordered by cysteine residues that may be functionally important. Images PMID:2951738

Thermophilic and alkaliphilic lipases are meeting a growing global attention as their increased importance in several industrial fields. Over 23 bacterial strains, novel strain with high lipolytic activity was isolated from Southern Sinai, Egypt, and it was identified as Geobacillus thermoleovorans DA2 using 16S rRNA as well as morphological and biochemical features. The lipase was produced in presence of fatty restaurant wastes as an inducing substrate. The optimized conditions for lipase production were recorded to be temperature 60°C, pH 10, and incubation time for 48 hrs. Enzymatic production increased when the organism was grown in a medium containing galactose as carbon source and ammonium phosphate as nitrogen source at concentrations of 1 and 0.5% (w/v), respectively. Moreover, the optimum conditions for lipase production such as substrate concentration, inoculum size, and agitation rate were found to be 10% (w/v), 4% (v/v), and 120 rpm, respectively. The TA lipase with Triton X-100 had the best degreasing agent by lowering the total lipid content to 2.6% as compared to kerosene (7.5%) or the sole crude enzyme (8.9%). It can be concluded that the chemical leather process can be substituted with TA lipase for boosting the quality of leather and reducing the environmental hazards. PMID:26881066

An analysis of new photometric and spectroscopic observations of the pulsating DA white dwarf GD 66 is presented. It is shown that the mode identification suggested by Dolez, Vauclair, and Chevreton (1983) is premature. The photometric data reveal the existence of several additional pulsation frequencies which do not fit with their model. Moreover, the 3.90 mHz peak seen in the Fourier spectrum of their light curve of GD 66 is shown to be an artifact of both insufficient time resolution and rotational splitting of the frequency of the dominant pulsation mode. It is not caused by the presence of an independent (different k value) pulsation mode as suggested. In addition, a comparison of model atmosphere calculations with the spectroscopic observations suggests that the surface gravity of GD 66 is quite normal (log g = 7.7 + 0.4 or - 0.2). This is in conflict with the model of the above authors which further requires a significantly larger surface gravity (log g equal to approximately 8.45) to account for the observed pulsation properties of GD 66.

Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD) can ameliorate the severity of acute pancreatitis (AP). However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight) orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively. Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10) and proinflammatory markers (tumor necrosis factor α and interleukin-6) and ameliorating the pathological damage in target tissues (P < 0.05). Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components. PMID:26199633

We have studied the effects of various Kampo medicines on P-glycoprotein (P-gp), a drug transporter, in vitro. The present study focused on Daiokanzoto (Da-Huang-Gan-Cao-Tang), which shows the most potent inhibitory effects on P-gp among the 50 Kampo medicines studied, and investigated the P-gp inhibitory effects of Daiokanzoto herbal ingredients (rhubarb and licorice root) and their components by an ATPase assay using human P-gp membrane. Both rhubarb and licorice root significantly inhibited ATPase activity, and the effects of rhubarb were more potent than those of licorice root. The content of rhubarb in Daiokanzoto is double that in licorice root, and the inhibition patterns of Daiokanzoto and rhubarb involve both competitive and noncompetitive inhibition, suggesting that the inhibitory effects of Daiokanzoto are mainly due to rhubarb. Concerning the components of rhubarb, concentration-dependent inhibitory effects were observed for (−)-catechin gallate, (−)-epicatechin gallate, and (−)-epigallocatechin gallate. In conclusion, rhubarb may cause changes in the drug dispositions of P-gp substrates through the inhibition of P-gp. It appears that attention should be given to the interactions between these drugs and Kampo medicines containing rhubarb as an herbal ingredient. PMID:22969825

All cells contain an enormous variety of ribonucleoprotein complexes that function in diverse processes. Although the mechanisms by which many of these RNPs contribute to cell metabolism are well understood, the roles of others are only now beginning to be revealed. A member of this latter category, the Ro 60 kDa protein and its associated noncoding Y RNAs, was discovered because the protein component is a frequent target of the autoimmune response in patients with the rheumatic diseases systemic lupus erythematosus and Sjögren’s syndrome. Recent studies have shown that Ro is ring-shaped, binds the single-stranded ends of misfolded noncoding RNAs in its central cavity, and may function in noncoding RNA quality control. Although Ro is not present in yeast, many bacterial genomes contain potential Ro orthologs. In the radiation-resistant eubacterium Deinococcus radiodurans, the Ro ortholog functions with exoribonucleases during stress-induced changes in RNA metabolism. Moreover, in both D. radiodurans and animal cells, Ro is involved in the response to multiple types of environmental stress. Finally, Y RNAs can influence the subcellular location of Ro, inhibit access of the central cavity to other RNAs and may also act as binding sites for proteins that influence Ro function. PMID:21823229

Nucleoporin 88 kDa (Nup88) is a tumor marker, overexpressed in various types of cancer. In Drosophila Nup88 (mbo) was reported to selectively mediate the nucleocytoplasmic transport of NF-{kappa}B, an ubiquitous transcription factor involved in immune responses, apoptosis, and cancer. We addressed the function of Nup88 in mammalian cells. Selective depletion of Nup88 by small interfering RNA (siRNA) inhibited NF-{kappa}B-dependent reporter gene activation and the nuclear translocation of NF-{kappa}B without affecting the upstream activation pathway in NIH3T3 cells. In contrast, nuclear translocation of glucocorticoid receptor was not reduced by the depletion of Nup88. In metastatic melanoma cells overexpressing Nup88, constitutive activation of NF-{kappa}B was found both in nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear accumulation of NF-{kappa}B subunits. We conclude that Nup88 regulates the activity of NF-{kappa}B at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-{kappa}B activation.

Minas Gerais is the major coffee-producing state of Brazil, with 28% of its production coming from the region of Zona da Mata. Four major species of root-knot nematode attacking coffee (Meloidogyne incognita, M. paranaensis, M. coffeicola, and M. exigua) have been reported from Brazil. To determine the variability in Meloidogyne spp. occurring in that region, 57 populations from 20 localities were evaluated for morphological, enzymatic, and physiological characteristics. According to the perineal pattern, all the populations were identified as M. exigua; however populations from the municipality of São João do Manhuaçu exhibited patterns very similar to M. arenaria. The identity of all the populations was confirmed by the phenotypes of esterase, malate dehydrogenase, superoxide dismutase, and glutamate-oxaloacetate transaminase. Thirteen populations (22.8%) showed the typical one-band (E1) esterase phenotype, whereas the others (77.2%) had a novel two-band phenotype (E2). No intraspecies variability was found in any population. All populations were able to reproduce on tomato, pepper, beans, cacao, and soybean. Reproduction was greater on tomato and pepper than on coffee seedlings, the susceptible standard. PMID:19262880

Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder. It is characterized by inflammatory symptoms, and interleukin (IL)-6 contributes to the disease pathogenesis. Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD, although the etiology of HHV-8-negative MCD is idiopathic (iMCD). A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been reported as TAFRO-iMCD, however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established. We retrospectively compared levels of serum interferon γ-induced protein 10 kDa (IP-10), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-10, and other cytokines between 11 cases of TAFRO-iMCD, 6 cases of plasma cell type iMCD, and 21 healthy controls. During flare-ups, patients with TAFRO-iMCD had significantly higher serum IP-10 and tended to have lower PDGF-AA levels than the other 2 groups. In addition, serum IL-10, IL-23, and vascular endothelial growth factor-A were elevated in both TAFRO-iMCD and iMCD. Elevated serum IP-10 is associated with inflammatory diseases including infectious diseases. There was a strong correlation between high serum IP-10 and the presence of TAFRO-iMCD, suggesting that IP-10 might be involved in the pathogenesis of TAFRO-iMCD.

Translocator protein (TSPO) is an 18-kDa high affinity cholesterol- and drug-binding protein found primarily in the outer mitochondrial membrane. Although TSPO is found in many tissue types, it is expressed at the highest levels under normal conditions in tissues that synthesize steroids. TSPO has been associated with cholesterol import into mitochondria, a key function in steroidogenesis, and directly or indirectly with multiple other cellular functions including apoptosis, cell proliferation, differentiation, anion transport, porphyrin transport, heme synthesis, and regulation of mitochondrial function. Aberrant expression of TSPO has been linked to multiple diseases, including cancer, brain injury, neurodegeneration, and ischemia reperfusion injury. There has been an effort during the last decade to understand the mechanisms regulating tissue- and disease-specific TSPO expression and to identify pharmacological means to control its expression. This review focuses on the current knowledge regarding the chemicals, hormones, and molecular mechanisms regulating Tspo gene expression under physiological conditions in a tissue- and disease-specific manner. The results described here provide evidence that the PKCε-ERK1/2-AP1/Stat3 signal transduction pathway is the primary regulator of Tspo gene expression in normal and pathological tissues expressing high levels of TSPO. PMID:20600583

A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8198553

Top-down proteomics is capable of identifying and quantitating unique proteoforms through the analysis of intact proteins. We extended the coverage of the label-free technique, achieving differential analysis of whole proteins <30 kDa from the proteomes of growing and senescent human fibroblasts. By integrating improved control software with more instrument time allocated for quantitation of intact ions, we were able to collect protein data between the two cell states, confidently comparing 1577 proteoform levels. To then identify and characterize proteoforms, our advanced acquisition software, named Autopilot, employed enhanced identification efficiency in identifying 1180 unique Swiss-Prot accession numbers at 1% false-discovery rate. This coverage of the low mass proteome is equivalent to the largest previously reported but was accomplished in 23% of the total acquisition time. By maximizing both the number of quantified proteoforms and their identification rate in an integrated software environment, this work significantly advances proteoform-resolved analyses of complex systems. PMID:26795204

The handedness of Leonardo da Vinci is controversial. Although there is little doubt that many of his well-attributed drawings were drawn with the left hand, the hatch marks of the shading going downwards from left to right, it is not clear that he was a natural left-hander, there being some suggestion that he may have become left-handed as the result of an injury to his right hand in early adulthood. Leonardo's lateralisation may be illuminated by an obscure passage in his notebooks in which he describes crouching down to look into a dark cave, putting his left hand on his knee, and shading his eyes with his right hand. We carried out a questionnaire survey, using 33 written and photographic items, to find whether this behaviour was typical of right handers or left handers. In fact the 'Leonardo task' showed almost no direct association with handedness, meaning that it contributes little to the immediate problem of elucidating Leonardo's handedness. However, the lateralisation of the task did relate to other aspects of behavioural laterality in surprisingly complex ways. This suggests that individual differences in handedness, and behavioural laterality in general, have a structural complexity which is not fully encompassed by simple measures of direction or degree of handedness.

What can be learned from historical anatomical drawings and how to incorporate these drawings into anatomical teaching? The drawing "A skull sectioned" (RL 19058v) by Leonardo da Vinci (1452-1519), hides more detailed information than reported earlier. A well-chosen section cut explores sectioned paranasal sinuses and ductus nasolacrimalis. A dissected lateral wall of the maxilla is also present. Furthermore, at the level of the foramen mentale, the drawing displays compact and spongious bony components, together with a cross-section through the foramen mentale and its connection with the canalis mandibulae. Leonardo was the first to describe a correct dental formula (6424) and made efforts to place this formula above the related dental elements. However, taking into account, the morphological features of the individual elements of the maxilla, it can be suggested that Leonardo sketched a "peculiar dental element" on the position of the right maxillary premolar in the dental sketch. The fact that the author did not make any comment on that special element is remarkable. Leonardo could have had sufficient knowledge of the precise morphology of maxillary and mandibular premolars, since the author depicted these elements in the dissected skull. The fact that the author also had access to premolars in situ corroborates our suggestion that "something went wrong" in this part of the drawing. The present study shows that historical anatomical drawings are very useful for interactive learning of detailed anatomy for students in medicine and dentistry.

The problems of nonradiative heating of outer atmospheric layers and p-mode oscillations in white dwarfs caused by acoustic waves generated in convective zones are discussed. These effects have been studied by calculating the cutoff periods for adiabatic and isothermal waves propagating in atmospheres of DA and DB stars with Teff greater than or equal 20,000 K and log g = 6-9. The obtained cutoff periods are approximately bounded by 0.01 and 40 sec for high- and low-gravity white dwarfs, respectively. Expected amplitudes of p-mode oscillations corresponding to trapped acoustic waves with small angular wave numbers are estimated, indicating that the amplitudes could be observed as Doppler shifts of spectral lines which might be detectable if adequate spectral resolution were available. The luminosity variations corresponding to these amplitudes are unlikely to be observable when all damping processes are accounted for. Results also indicate that the present theory of convection predicts some irregularities in the behavior of physical parameters. 34 refs.

The problems of nonradiative heating of outer atmospheric layers and p-mode oscillations in white dwarfs caused by acoustic waves generated in convective zones are discussed. These effects have been studied by calculating the cutoff periods for adiabatic and isothermal waves propagating in atmospheres of DA and DB stars with Teff greater than or equal 20,000 K and log g = 6-9. The obtained cutoff periods are approximately bounded by 0.01 and 40 sec for high- and low-gravity white dwarfs, respectively. Expected amplitudes of p-mode oscillations corresponding to trapped acoustic waves with small angular wave numbers are estimated, indicating that the amplitudes could be observed as Doppler shifts of spectral lines which might be detectable if adequate spectral resolution were available. The luminosity variations corresponding to these amplitudes are unlikely to be observable when all damping processes are accounted for. Results also indicate that the present theory of convection predicts some irregularities in the behavior of physical parameters.

A low molecular weight acid phosphatase was purified to homogeneity from chicken heart with a specific activity of 42 U/mg and a recovery of about 1%. Nearly 800 fold purification was achieved. The molecular weight was estimated to be 18 kDa by SDS-polyacrylamide gel electrophoresis. Para-nitrophenyl phosphate, phenyl phosphate and flavin mononucleotide were efficiently hydrolysed by the enzyme and found to be good substrates. Fluoride and tartrate had no inhibitory effect while phosphate, vanadate and molybdate strongly inhibited the enzyme. The acid phosphatase was stimulated in the presence of glycerol, ethylene glycol, methanol, ethanol and acetone, which reflected the phosphotransferase activity. When phosphate acceptors such as ethylene glycol concentrations were increased, the ratio of phosphate transfer to hydrolysis was also increased, demonstrating the presence of a transphosphorylation reaction where an acceptor can compete with water in the rate limiting step involving hydrolysis of a covalent phospho enzyme intermediate. Partition experiments carried out with two substrates, para-nitrophenyl phosphate and phenyl phosphate, revealed a constant product ratio of 1.7 for phosphotransfer to ethylene glycol versus hydrolysis, strongly supporting the existence of common covalent phospho enzyme intermediate. A constant ratio of K (cat)/K (m), 4.3 x 10(4), found at different ethylene glycol concentrations, also supported the idea that the rate limiting step was the hydrolysis of the phospho enzyme intermediate.

The KLOE experiment is currently taking data at the electron-positron collider DA{phi}NE, the Frascati {phi}-factory. At the end of this run, we expect to have integrated 2.5 fb-1 of collisions at center of mass energy W {approx} M{phi}. Large samples of light pseudoscalar and scalar mesons are produced through {phi} radiative decays. A summary of the measurements in progress on the previously collected 450 pb-1 allows us to quote the expectations on the entire sample. KLOE has also proven the feasibility of precise measurement of the hadronic cross-section {sigma}(e+e- {yields} {pi}+{pi}-) in the region 0.33 < M{sub {pi}}{sub {pi}}{sup 2} < 1.02 GeV{sup 2}, extracting it by the measurement of the {pi}+{pi}-{gamma} cross section at small photon angles. Prospects for the entire sample and the feasibility to extend such a measurement down to threshold are presented.

Chimeric avidin (ChiAVD) is a product of rational protein engineering remarkably resistant to heat and harsh conditions. In quest of the fundamentals behind factors affecting stability we have elucidated the solution NMR spectroscopic structure of the biotin-bound form of ChiAVD and characterized the protein dynamics through 15N relaxation and hydrogen/deuterium (H/D) exchange of this and the biotin-free form. To surmount the challenges arising from the very large size of the protein for NMR spectroscopy, we took advantage of its high thermostability. Conventional triple resonance experiments for fully protonated proteins combined with methyl-detection optimized experiments acquired at 58°C were adequate for the structure determination of this 56 kDa protein. The model-free parameters derived from the 15N relaxation data reveal a remarkably rigid protein at 58°C in both the biotin-bound and the free forms. The H/D exchange experiments indicate a notable increase in hydrogen protection upon biotin binding.

Rhubarb (Rheum tanguticum; da-huang in Chinese medicine) is a herbal medicine that has been used widely for managing fever and removing toxicity. In this study, we investigated how rhubarb inhibits influenza virus during the early stage of the infectious cycle using different functional assays. A non-toxic ethanolic extract of rhubarb (Rex) inhibited several H1N1 subtypes of influenza A viruses in Madin–Darby canine kidney cells, including strains that are clinically resistant to oseltamivir. Time course analysis of Rex addition showed that viral entry was one of the steps that was inhibited by Rex. We also confirmed that Rex effectively inhibited viral attachment and penetration into the host cells. The inhibition of red blood cell haemolysis and cell–cell fusion by Rex suggests that Rex may block haemagglutinin-mediated fusion (virus–endosome fusion) during the fusion/uncoating step. Rex has the capacity to inhibit influenza viruses by blocking viral endocytosis. Thus, rhubarb might provide an alternative therapeutic approach when resistant viruses become more prevalent. PMID:27302738

Previous reports have shown that catecholamine regulated proteins (CRP) are central nervous system specific and covalently bind to catecholamines. In the present study, we report the subcellular localization and differential modulation of a 40-kDa catecholamine regulated protein (CRP40) by dopamine D1 and D2 receptor antagonists. CRP40 was found to be localized with nuclear and synaptosomal/mitochondrial and fractions. Chronic treatment with dopamine D2 receptor antagonist haloperidol in rats significantly increased the levels of CRP40 in the striatum, whereas, chronic R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) dopamine D1 receptor antagonist administration significantly decreased striatal CRP40 levels. Moreover, acute haloperidol treatment did not alter the levels of CRP40 in any of the brain regions. Despite a sequence homology with the heat shock protein 70 (HSP70), levels of HSP70 remained unchanged after either drug treatment, suggesting a distinct function of CRP40 than HSP70. These results further suggest that CRP40 play an important role in dopaminergic neuronal function and the dopamine D1 receptor-mediated signaling pathway may be involved in the regulation of CRP40.

CARMENES, the new ultra-stable high-resolution spectrograph at the 3.5 m Calar Alto telescope and the only one in its category that covers from 0.52 to 1.71μm in one shot, started its guaranteed time observations (GTO) in January 2016. Under GTO, CARMENES is monitoring approximately 300 selected M dwarfs for at least three years with the aim of finding rocky planets, perhaps habitable, orbiting around them. Those 300 GTO stars are the brightest and latest single M dwarfs observable from Calar Alto, which are carefully picked up from the CARMENES input catalogue, dubbed ''Carmencita'': CARMENES Cool star Information and daTa Archive. For each of the over 2200 M dwarfs in Carmencita, a team of German and Spanish astronomers involving PhD, MSc and BSc students has collected a large amount of information, compiled from the literature or measured by us with new data: accurate astrometry, spectral typing, photometry in 19 bands from the ultraviolet to the mid-infrared, rotational and radial velocities, X-ray count rates and hardness ratios, close and wide multiplicity data, kinematics, derived stellar parameters... The private online catalogue, including preparatory science observations (i.e., high-resolution imaging, low-and high-resolution spectroscopy), will be eventually public as a CARMENES legacy.